EC 6.1.1.1     
Accepted name: tyrosine—tRNA ligase
Reaction: ATP + L-tyrosine + tRNATyr = AMP + diphosphate + L-tyrosyl-tRNATyr
Systematic name: L-tyrosine:tRNATyr ligase (AMP-forming)
References:
1.  Allen, E.H., Glassman, E. and Schweet, R.S. Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes. J. Biol. Chem. 235 (1960) 1061–1067. [PMID: 13792726]
2.  Cowles, J.R. and Key, J.L. Demonstration of two tyrosyl-tRNA synthetases of pea roots. Biochim. Biophys. Acta 281 (1972) 33–44. [PMID: 4563531]
3.  Holley, R.W., Brunngraber, E.F., Saad, F. and Williams, H.H. Partial purification of the threonine- and tyrosine-activating enzymes from rat liver, and the effect of potassium ions on the activity of the tyrosine enzyme. J. Biol. Chem. 236 (1961) 197–199. [PMID: 13715350]
4.  Schweet, R.S. and Allen, E.H. Purification and properties of tyrosine-activating enzyme of hog pancreas. J. Biol. Chem. 233 (1958) 1104–1108. [PMID: 13598741]
5.  Brick, P., Bhat, T.N. and Blow, D.M. Structure of tyrosyl-tRNA synthetase refined at 2.3 Å resolution. Interaction of the enzyme with the tyrosyl adenylate intermediate. J. Mol. Biol. 208 (1989) 83–98. [PMID: 2504923]
[EC 6.1.1.1 created 1961, modified 2002]
 
 
EC 6.1.1.2     
Accepted name: tryptophan—tRNA ligase
Reaction: ATP + L-tryptophan + tRNATrp = AMP + diphosphate + L-tryptophyl-tRNATrp
Other name(s): tryptophanyl-tRNA synthetase; L-tryptophan-tRNATrp ligase (AMP-forming); tryptophanyl-transfer ribonucleate synthetase; tryptophanyl-transfer ribonucleic acid synthetase; tryptophanyl-transfer RNA synthetase; tryptophanyl ribonucleic synthetase; tryptophanyl-transfer ribonucleic synthetase; tryptophanyl-tRNA synthase; tryptophan translase; TrpRS
Systematic name: L-tryptophan:tRNATrp ligase (AMP-forming)
References:
1.  Davie, E.W., Koningsberger, V.V. and Lipmann, F. The isolation of a tryptophan-activating enzyme from pancreas. Arch. Biochem. Biophys. 65 (1956) 21–28. [PMID: 13373404]
2.  Preddie, E.C. Tryptophanyl transfer ribonucleic acid synthetase from bovine pancreas. II. The chemically different subunits. J. Biol. Chem. 244 (1969) 3958–3968. [PMID: 5805407]
3.  Wong, K.K., Meister, A. and Moldave, K. Enzymic formation of ribonucleic acid-amino acid from synthetic aminoacyladenylate and ribonucleic acid. Biochim. Biophys. Acta 36 (1959) 531–533. [PMID: 13845797]
[EC 6.1.1.2 created 1961, modified 2002]
 
 
EC 6.1.1.3     
Accepted name: threonine—tRNA ligase
Reaction: ATP + L-threonine + tRNAThr = AMP + diphosphate + L-threonyl-tRNAThr
Other name(s): threonyl-tRNA synthetase; threonyl-transfer ribonucleate synthetase; threonyl-transfer RNA synthetase; threonyl-transfer ribonucleic acid synthetase; threonyl ribonucleic synthetase; threonine-transfer ribonucleate synthetase; threonine translase; threonyl-tRNA synthetase; TRS
Systematic name: L-threonine:tRNAThr ligase (AMP-forming)
References:
1.  Allen, E.H., Glassman, E. and Schweet, R.S. Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes. J. Biol. Chem. 235 (1960) 1061–1067. [PMID: 13792726]
2.  Holley, R.W., Brunngraber, E.F., Saad, F. and Williams, H.H. Partial purification of the threonine- and tyrosine-activating enzymes from rat liver, and the effect of potassium ions on the activity of the tyrosine enzyme. J. Biol. Chem. 236 (1961) 197–199. [PMID: 13715350]
[EC 6.1.1.3 created 1961]
 
 
EC 6.1.1.4     
Accepted name: leucine—tRNA ligase
Reaction: ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu
Other name(s): leucyl-tRNA synthetase; leucyl-transfer ribonucleate synthetase; leucyl-transfer RNA synthetase; leucyl-transfer ribonucleic acid synthetase; leucine-tRNA synthetase; leucine translase
Systematic name: L-leucine:tRNALeu ligase (AMP-forming)
References:
1.  Allen, E.H., Glassman, E. and Schweet, R.S. Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes. J. Biol. Chem. 235 (1960) 1061–1067. [PMID: 13792726]
2.  Berg, P., Bergmann, F.H., Ofengand, E.J. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. I. The mechanism of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid formation. J. Biol. Chem. 236 (1961) 1726–1734.
3.  Bergmann, F.H., Berg, P. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. II. The preparation of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid synthetases from Escherichia coli. J. Biol. Chem. 236 (1961) 1735–1740.
[EC 6.1.1.4 created 1961]
 
 
EC 6.1.1.5     
Accepted name: isoleucine—tRNA ligase
Reaction: ATP + L-isoleucine + tRNAIle = AMP + diphosphate + L-isoleucyl-tRNAIle
Other name(s): isoleucyl-tRNA synthetase; isoleucyl-transfer ribonucleate synthetase; isoleucyl-transfer RNA synthetase; isoleucine-transfer RNA ligase; isoleucine-tRNA synthetase; isoleucine translase
Systematic name: L-isoleucine:tRNAIle ligase (AMP-forming)
References:
1.  Allen, E.H., Glassman, E. and Schweet, R.S. Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes. J. Biol. Chem. 235 (1960) 1061–1067. [PMID: 13792726]
2.  Berg, P., Bergmann, F.H., Ofengand, E.J. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. I. The mechanism of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid formation. J. Biol. Chem. 236 (1961) 1726–1734.
3.  Bergmann, F.H., Berg, P. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. II. The preparation of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid synthetases from Escherichia coli. J. Biol. Chem. 236 (1961) 1735–1740.
[EC 6.1.1.5 created 1961]
 
 
EC 6.1.1.6     
Accepted name: lysine—tRNA ligase
Reaction: ATP + L-lysine + tRNALys = AMP + diphosphate + L-lysyl-tRNALys
Other name(s): lysyl-tRNA synthetase; lysyl-transfer ribonucleate synthetase; lysyl-transfer RNA synthetase; L-lysine-transfer RNA ligase; lysine-tRNA synthetase; lysine translase
Systematic name: L-lysine:tRNALys ligase (AMP-forming)
References:
1.  Allen, E.H., Glassman, E. and Schweet, R.S. Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes. J. Biol. Chem. 235 (1960) 1061–1067. [PMID: 13792726]
2.  Chiumecka, V., von Tigerstrom, M., D'Obrenan, P. and Smith, C.J. Purification and properties of lysyl transfer ribonucleic acid synthetase from bakers' yeast. J. Biol. Chem. 244 (1969) 5481–5488. [PMID: 4310598]
3.  Lagerkvist, U., Rymo, L., Lindqvist, O. and Andersson, E. Some properties of crystals of lysine transfer ribonucleic acid ligase from yeast. J. Biol. Chem. 247 (1972) 3897–3899. [PMID: 4555953]
4.  Stern, R. and Mehler, A.H. Lysyl-sRNA synthetase from Escherichia coli. Biochem. Z. 342 (1965) 400–409. [PMID: 4284804]
[EC 6.1.1.6 created 1961]
 
 
EC 6.1.1.7     
Accepted name: alanine—tRNA ligase
Reaction: ATP + L-alanine + tRNAAla = AMP + diphosphate + L-alanyl-tRNAAla
Other name(s): alanyl-tRNA synthetase; alanyl-transfer ribonucleate synthetase; alanyl-transfer RNA synthetase; alanyl-transfer ribonucleic acid synthetase; alanine-transfer RNA ligase; alanine transfer RNA synthetase; alanine tRNA synthetase; alanine translase; alanyl-transfer ribonucleate synthase; AlaRS; Ala-tRNA synthetase
Systematic name: L-alanine:tRNAAla ligase (AMP-forming)
References:
1.  Holley, R.W. and Goldstein, J. An alanine-dependent, ribonuclease-inhibited conversion of adenosine 5′-phosphate to adenosine triphosphate. J. Biol. Chem. 234 (1959) 1765–1768. [PMID: 13672960]
2.  Webster, G.C. Isolation of an alanine-activating enzyme from pig liver. Biochim. Biophys. Acta 49 (1961) 141–152. [PMID: 13783653]
[EC 6.1.1.7 created 1961]
 
 
EC 6.1.1.8      
Deleted entry:  D-alanine-sRNA synthetase
[EC 6.1.1.8 created 1961, deleted 1965]
 
 
EC 6.1.1.9     
Accepted name: valine—tRNA ligase
Reaction: ATP + L-valine + tRNAVal = AMP + diphosphate + L-valyl-tRNAVal
Other name(s): valyl-tRNA synthetase; valyl-transfer ribonucleate synthetase; valyl-transfer RNA synthetase; valyl-transfer ribonucleic acid synthetase; valine transfer ribonucleate ligase; valine translase
Systematic name: L-valine:tRNAVal ligase (AMP-forming)
References:
1.  Berg, P., Bergmann, F.H., Ofengand, E.J. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. I. The mechanism of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid formation. J. Biol. Chem. 236 (1961) 1726–1734.
2.  Bergmann, F.H., Berg, P. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. II. The preparation of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid synthetases from Escherichia coli. J. Biol. Chem. 236 (1961) 1735–1740.
[EC 6.1.1.9 created 1961]
 
 
EC 6.1.1.10     
Accepted name: methionine—tRNA ligase
Reaction: ATP + L-methionine + tRNAMet = AMP + diphosphate + L-methionyl-tRNAMet
Other name(s): methionyl-tRNA synthetase; methionyl-transfer ribonucleic acid synthetase; methionyl-transfer ribonucleate synthetase; methionyl-transfer RNA synthetase; methionine translase; MetRS
Systematic name: L-methionine:tRNAMet ligase (AMP-forming)
Comments: In those organisms producing N-formylmethionyl-tRNAfMet for translation initiation, this enzyme also recognizes the initiator tRNAfMet and catalyses the formation of L-methionyl-tRNAfMet, the substrate for EC 2.1.2.9, methionyl-tRNA formyltransferase.
References:
1.  Bergmann, F.H., Berg, P. and Dieckmann, M. The enzymic synthesis of amino acyl derivatives of ribonucleic acid. II. The preparation of leucyl-, valyl-, isoleucyl- and methionyl ribonucleic acid synthetases from Escherichia coli. J. Biol. Chem. 236 (1961) 1735–1740.
2.  Lee, C.P., Dyson, M.R., Mandal, N., Varshney, U., Bahramian, B. and RajBhandary, U.L. Striking effects of coupling mutations in the acceptor stem on recognition of tRNAs by Escherichia coli Met-tRNA synthetase and Met-tRNA transformylase. Proc. Natl. Acad. Sci. USA 89 (1992) 9262–9266. [PMID: 1409632]
[EC 6.1.1.10 created 1961, modified 2002]
 
 
EC 6.1.1.11     
Accepted name: serine—tRNA ligase
Reaction: ATP + L-serine + tRNASer = AMP + diphosphate + L-seryl-tRNASer
Other name(s): seryl-tRNA synthetase; SerRS; seryl-transfer ribonucleate synthetase; seryl-transfer RNA synthetase; seryl-transfer ribonucleic acid synthetase; serine translase
Systematic name: L-serine:tRNASer ligase (AMP-forming)
Comments: This enzyme also recognizes tRNASec, the special tRNA for selenocysteine, and catalyses the formation of L-seryl-tRNASec, the substrate for EC 2.9.1.1, L-seryl-tRNASec selenium transferase.
References:
1.  Katze, J.R. and Konigsberg, W. Purification and properties of seryl transfer ribonucleic acid synthetase from Escherichia coli. J. Biol. Chem. 245 (1970) 923–930. [PMID: 4906848]
2.  Makman, M.H. and Cantoni, G.L. Isolation of seryl and phenylalanyl ribonucleic acid synthetases from baker's yeast. Biochemistry 4 (1965) 1434–1442.
3.  Webster, L.T. and Davie, E.W. Purification and properties of serine-activating enzyme from beef pancreas. J. Biol. Chem. 236 (1961) 479–484. [PMID: 13783661]
4.  Ohama, T., Yang, D.C. and Hatfield, D.L. Selenocysteine tRNA and serine tRNA are aminoacylated by the same synthetase, but may manifest different identities with respect to the long extra arm. Arch. Biochem. Biophys. 315 (1994) 293–301. [PMID: 7986071]
[EC 6.1.1.11 created 1961, modified 2002]
 
 
EC 6.1.1.12     
Accepted name: aspartate—tRNA ligase
Reaction: ATP + L-aspartate + tRNAAsp = AMP + diphosphate + L-aspartyl-tRNAAsp
Other name(s): aspartyl-tRNA synthetase; aspartyl ribonucleic synthetase; aspartyl-transfer RNA synthetase; aspartic acid translase; aspartyl-transfer ribonucleic acid synthetase; aspartyl ribonucleate synthetase
Systematic name: L-aspartate:tRNAAsp ligase (AMP-forming)
References:
1.  Gangloff, J. and Dirheimer, G. Studies on aspartyl-tRNA synthetase from baker's yeast. I. Purification and properties of the enzyme. Biochim. Biophys. Acta 294 (1973) 263–272. [PMID: 4575961]
2.  Norton, S.J., Ravel, J.M., Lee, C. and Shive, W. Purification and properties of the aspartyl ribonucleic acid synthetase of Lactobacillus arabinosus. J. Biol. Chem. 238 (1963) 269–274. [PMID: 13939000]
[EC 6.1.1.12 created 1965]
 
 
EC 6.1.1.13     
Accepted name: D-alanine—poly(phosphoribitol) ligase
Reaction: ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate)
Other name(s): D-alanyl-poly(phosphoribitol) synthetase; D-alanine: membrane acceptor ligase; D-alanine-D-alanyl carrier protein ligase; D-alanine-membrane acceptor ligase; D-alanine-activating enzyme
Systematic name: D-alanine:poly(phosphoribitol) ligase (AMP-forming)
Comments: A thioester bond is formed transiently between D-alanine and the sulfhydryl group of the 4′-phosphopantetheine prosthetic group of D-alanyl carrier protein during the activation of the alanine. Involved in the synthesis of teichoic acids.
References:
1.  Baddiley, J. and Neuhaus, F.C. The enzymic activation of D-alanine. Biochem. J. 75 (1960) 579. [PMID: 13795638]
2.  Reusch, V.M. and Neuhaus, F.C. D-Alanine:membrane acceptor ligase from Lactobacillus casei. J. Biol. Chem. 246 (1971) 6136–6143. [PMID: 4399593]
3.  Perego, M., Glaser, P., Minutello, A., Strauch, M.A., Leopold, K. and Fischer, W. Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. J. Biol. Chem. 270 (1995) 15598–15606. [PMID: 7797557]
4.  Heaton, M.P. and Neuhaus, F.C. Role of D-alanyl carrier protein in the biosynthesis of D-alanyl-lipoteichoic acid. J. Bacteriol. 176 (1994) 681–690. [PMID: 8300523]
5.  Debabov, D.V., Heaton, M.P., Zhang, Q., Stewart, K.D., Lambalot, R.H. and Neuhaus, F.C. The D-alanyl carrier protein in Lactobacillus casei: cloning, sequencing and expression of dltC. J. Bacteriol. 178 (1996) 3869–3876. [PMID: 8682792]
[EC 6.1.1.13 created 1965, modified 2001]
 
 
EC 6.1.1.14     
Accepted name: glycine—tRNA ligase
Reaction: ATP + glycine + tRNAGly = AMP + diphosphate + glycyl-tRNAGly
Other name(s): glycyl-tRNA synthetase; glycyl-transfer ribonucleate synthetase; glycyl-transfer RNA synthetase; glycyl-transfer ribonucleic acid synthetase; glycyl translase
Systematic name: glycine:tRNAGly ligase (AMP-forming)
References:
1.  Fraser, M.J. Glycyl-RNA synthetase of rat liver: partial purification and effects of some metal ions on its activity. Can. J. Biochem. Physiol. 41 (1963) 1123–1233. [PMID: 13959340]
2.  Niyomporn, B., Dahl, J.L. and Strominger, J.L. Biosynthesis of the peptidoglycan of bacterial cell walls. IX. Purification and properties of glycyl transfer ribonucleic acid synthetase from Staphylococcus aureus. J. Biol. Chem. 243 (1968) 773–778. [PMID: 4295604]
[EC 6.1.1.14 created 1972]
 
 
EC 6.1.1.15     
Accepted name: proline—tRNA ligase
Reaction: ATP + L-proline + tRNAPro = AMP + diphosphate + L-prolyl-tRNAPro
Other name(s): prolyl-tRNA synthetase; prolyl-transferRNA synthetase; prolyl-transfer ribonucleate synthetase; proline translase; prolyl-transfer ribonucleic acid synthetase; prolyl-s-RNA synthetase; prolinyl-tRNA ligase
Systematic name: L-proline:tRNAPro ligase (AMP-forming)
References:
1.  Norton, S.J. Purification and properties of the prolyl RNA synthetase of Escherichia coli. Arch. Biochem. Biophys. 106 (1964) 147–152. [PMID: 14217147]
2.  Peterson, P.J. and Fowden, L. Purification, properties and comparative specificities of the enzyme prolyl-transfer ribonucleic acid synthetase from Phaseolus aureus and Polygonatum multiflorum. Biochem. J. 97 (1965) 112–124. [PMID: 16749091]
[EC 6.1.1.15 created 1972]
 
 
EC 6.1.1.16     
Accepted name: cysteine—tRNA ligase
Reaction: ATP + L-cysteine + tRNACys = AMP + diphosphate + L-cysteinyl-tRNACys
Other name(s): cysteinyl-tRNA synthetase; cysteinyl-transferRNA synthetase; cysteinyl-transfer ribonucleate synthetase; cysteine translase
Systematic name: L-cysteine:tRNACys ligase (AMP-forming)
References:
1.  McCorquodale, D.J. The separation and partial purification of aminoacyl-RNA synthetases from Escherichia coli. Biochim. Biophys. Acta 91 (1964) 541–548. [PMID: 14262440]
[EC 6.1.1.16 created 1972]
 
 
EC 6.1.1.17     
Accepted name: glutamate—tRNA ligase
Reaction: ATP + L-glutamate + tRNAGlu = AMP + diphosphate + L-glutamyl-tRNAGlu
Other name(s): glutamyl-tRNA synthetase; glutamyl-transfer ribonucleate synthetase; glutamyl-transfer RNA synthetase; glutamyl-transfer ribonucleic acid synthetase; glutamate-tRNA synthetase; glutamic acid translase
Systematic name: L-glutamate:tRNAGlu ligase (AMP-forming)
References:
1.  Ravel, J.M., Wang, S., Heinemeyer, C. and Shive, W. Glutamyl and glutaminyl ribonucleic acid synthetases of Escherichia coli W. Separation, properties, and stimulation of adenosine triphosphate-pyrophosphate exchange by acceptor ribonucleic acid. J. Biol. Chem. 240 (1965) 432–438. [PMID: 14253448]
[EC 6.1.1.17 created 1972]
 
 
EC 6.1.1.18     
Accepted name: glutamine—tRNA ligase
Reaction: ATP + L-glutamine + tRNAGln = AMP + diphosphate + L-glutaminyl-tRNAGln
Other name(s): glutaminyl-tRNA synthetase; glutaminyl-transfer RNA synthetase; glutaminyl-transfer ribonucleate synthetase; glutamine-tRNA synthetase; glutamine translase; glutamate-tRNA ligase; glutaminyl ribonucleic acid; GlnRS
Systematic name: L-glutamine:tRNAGln ligase (AMP-forming)
References:
1.  Ravel, J.M., Wang, S., Heinemeyer, C. and Shive, W. Glutamyl and glutaminyl ribonucleic acid synthetases of Escherichia coli W. Separation, properties, and stimulation of adenosine triphosphate-pyrophosphate exchange by acceptor ribonucleic acid. J. Biol. Chem. 240 (1965) 432–438. [PMID: 14253448]
[EC 6.1.1.18 created 1972]
 
 
EC 6.1.1.19     
Accepted name: arginine—tRNA ligase
Reaction: ATP + L-arginine + tRNAArg = AMP + diphosphate + L-arginyl-tRNAArg
Other name(s): arginyl-tRNA synthetase; arginyl-transfer ribonucleate synthetase; arginyl-transfer RNA synthetase; arginyl transfer ribonucleic acid synthetase; arginine-tRNA synthetase; arginine translase
Systematic name: L-arginine:tRNAArg ligase (AMP-forming)
References:
1.  Allende, C.C. and Allende, J.E. Purification and substrate specificity of arginyl-ribonucleic acid synthetase from rat liver. J. Biol. Chem. 239 (1964) 1102–1106. [PMID: 14165914]
2.  Mehler, A.H. and Mitra, S.K. The activation of arginyl transfer ribonucleic acid synthetase by transfer ribonucleic acid. J. Biol. Chem. 242 (1967) 5495–5499. [PMID: 12325365]
3.  Mitra, S.K. and Mehler, A.H. The arginyl transfer ribonucleic acid synthetase of Escherichia coli. J. Biol. Chem. 242 (1967) 5491–5494. [PMID: 12325364]
[EC 6.1.1.19 created 1972]
 
 
EC 6.1.1.20     
Accepted name: phenylalanine—tRNA ligase
Reaction: ATP + L-phenylalanine + tRNAPhe = AMP + diphosphate + L-phenylalanyl-tRNAPhe
Other name(s): phenylalanyl-tRNA synthetase; phenylalanyl-transfer ribonucleate synthetase; phenylalanine-tRNA synthetase; phenylalanyl-transfer RNA synthetase; phenylalanyl-tRNA ligase; phenylalanyl-transfer RNA ligase; L-phenylalanyl-tRNA synthetase; phenylalanine translase
Systematic name: L-phenylalanine:tRNAPhe ligase (AMP-forming)
References:
1.  Stulberg, M.P. The isolation and properties of phenylalanyl ribonucleic acid synthetase from Escherichia coli B. J. Biol. Chem. 242 (1967) 1060–1064. [PMID: 5335910]
[EC 6.1.1.20 created 1972]
 
 
EC 6.1.1.21     
Accepted name: histidine—tRNA ligase
Reaction: ATP + L-histidine + tRNAHis = AMP + diphosphate + L-histidyl-tRNAHis
Other name(s): histidyl-tRNA synthetase; histidyl-transfer ribonucleate synthetase; histidine translase
Systematic name: L-histidine:tRNAHis ligase (AMP-forming)
References:
1.  Tigerstrom, M.V. and Tener, G.M. Histidyl transfer ribonucleic acid synthetase from bakers' yeast. Can. J. Biochem. 45 (1967) 1067–1074. [PMID: 6035970]
[EC 6.1.1.21 created 1972]
 
 
EC 6.1.1.22     
Accepted name: asparagine—tRNA ligase
Reaction: ATP + L-asparagine + tRNAAsn = AMP + diphosphate + L-asparaginyl-tRNAAsn
Other name(s): asparaginyl-tRNA synthetase; asparaginyl-transfer ribonucleate synthetase; asparaginyl transfer RNA synthetase; asparaginyl transfer ribonucleic acid synthetase; asparagyl-transfer RNA synthetase; asparagine translase
Systematic name: L-asparagine:tRNAAsn ligase (AMP-forming)
References:
1.  Davies, M.R. and Marshall, R.D. Partial purification of L-asparginyl-tRNA synthetase from rabbit liver. Biochem. Biophys. Res. Commun. 47 (1972) 1386–1395. [PMID: 5040239]
[EC 6.1.1.22 created 1976]
 
 
EC 6.1.1.23     
Accepted name: aspartate—tRNAAsn ligase
Reaction: ATP + L-aspartate + tRNAAsx = AMP + diphosphate + L-aspartyl-tRNAAsx
Other name(s): nondiscriminating aspartyl-tRNA synthetase
Systematic name: L-aspartate:tRNAAsx ligase (AMP-forming)
Comments: When this enzyme acts on tRNAAsp, it catalyses the same reaction as EC 6.1.1.12, aspartate—tRNA ligase. It has, however, diminished discrimination, so that it can also form aspartyl-tRNAAsn. This relaxation of specificity has been found to result from the absence of a loop in the tRNA that specifically recognizes the third position of the anticodon [1]. This accounts for the ability of this enzyme in, for example, Thermus thermophilus, to recognize both tRNAAsp (GUC anticodon) and tRNAAsn (GUU anticodon). The aspartyl-tRNAAsn is not used in protein synthesis until it is converted by EC 6.3.5.6, asparaginyl-tRNA synthase (glutamine-hydrolysing), into asparaginyl-tRNAAsn.
References:
1.  Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617–650. [PMID: 10966471]
2.  Schmitt, E., Moulinier, L., Fujiwara, S., Imanaka, T., Thierry, J.C. and Moras, D. Crystal structure of aspartyl-tRNA synthetase from Pyrococcus kodakaraensis KOD: archaeon specificity and catalytic mechanism of adenylate formation. EMBO J. 17 (1998) 5227–5237. [PMID: 9724658]
3.  Becker, H.D. and Kern, D. Thermus thermophilus: a link in evolution of the tRNA-dependent amino acid amidation pathways. Proc. Natl. Acad. Sci. USA 95 (1998) 12832–12837. [PMID: 9789000]
[EC 6.1.1.23 created 2002]
 
 
EC 6.1.1.24     
Accepted name: glutamate—tRNAGln ligase
Reaction: ATP + L-glutamate + tRNAGlx = AMP + diphosphate + L-glutamyl-tRNAGlx
Other name(s): nondiscriminating glutamyl-tRNA synthetase
Systematic name: L-glutamate:tRNAGlx ligase (AMP-forming)
Comments: When this enzyme acts on tRNAGlu, it catalyses the same reaction as EC 6.1.1.17, glutamate—tRNA ligase. It has, however, diminished discrimination, so that it can also form glutamyl-tRNAGln. This relaxation of specificity has been found to result from the absence of a loop in the tRNA that specifically recognizes the third position of the anticodon [1]. This accounts for the ability of this enzyme in, for example, Bacillus subtilis, to recognize both tRNA1Gln (UUG anticodon) and tRNAGlu (UUC anticodon) but not tRNA2Gln (CUG anticodon). The ability of this enzyme to recognize both tRNAGlu and one of the tRNAGln isoacceptors derives from their sharing a major identity element, a hypermodified derivative of U34 (5-methylaminomethyl-2-thiouridine). The glutamyl-tRNAGln is not used in protein synthesis until it is converted by EC 6.3.5.7, glutaminyl-tRNA synthase (glutamine-hydrolysing), into glutaminyl-tRNAGln.
References:
1.  Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617–650. [PMID: 10966471]
2.  Schmitt, E., Moulinier, L., Fujiwara, S., Imanaka, T., Thierry, J.C. and Moras, D. Crystal structure of aspartyl-tRNA synthetase from Pyrococcus kodakaraensis KOD: archaeon specificity and catalytic mechanism of adenylate formation. EMBO J. 17 (1998) 5227–5237. [PMID: 9724658]
3.  Kim, S.I. and Söll, D. Major identity element of glutamine tRNAs from Bacillus subtilis and Escherichia coli in the reaction with B. subtilis glutamyl-tRNA synthetase. Mol. Cells 8 (1998) 459–465. [PMID: 9749534]
[EC 6.1.1.24 created 2002]
 
 
EC 6.1.1.25      
Deleted entry: lysine—tRNAPyl ligase. The tRNAPyl is now known only to be charged with pyrrolysine (cf. EC 6.1.1.26).
[EC 6.1.1.25 created 2002, deleted 2012]
 
 
EC 6.1.1.26     
Accepted name: pyrrolysine—tRNAPyl ligase
Reaction: ATP + L-pyrrolysine + tRNAPyl = AMP + diphosphate + L-pyrrolysyl-tRNAPyl
Glossary: pyrrolysine = N6-[(2R,3R)-3-methyl-3,4-dihydro-2H-pyrrol-2-ylcarbonyl]-L-lysine
Other name(s): PylS; pyrrolysyl-tRNA synthetase
Systematic name: L-pyrrolysine:tRNAPyl ligase (AMP-forming)
Comments: In organisms such as Methanosarcina barkeri that incorporate the modified amino acid pyrrolysine (Pyl) into certain methylamine methyltransferases, an unusual tRNAPyl, with a CUA anticodon, can be charged directly with pyrrolysine by this class II aminoacyl—tRNA ligase. The enzyme is specific for pyrrolysine as substrate as it cannot be replaced by lysine or any of the other natural amino acids [1].
References:
1.  Blight, S.K., Larue, R.C., Mahapatra, A., Longstaff, D.G., Chang, E., Zhao, G., Kang, P.T., Green-Church, K.B., Chan, M.K. and Krzycki, J.A. Direct charging of tRNA(CUA) with pyrrolysine in vitro and in vivo. Nature 431 (2004) 333–335. [PMID: 15329732]
2.  Polycarpo, C., Ambrogelly, A., Bérubé, A., Winbush, S.M., McCloskey, J.A., Crain, P.F., Wood, J.L. and Söll, D. An aminoacyl-tRNA synthetase that specifically activates pyrrolysine. Proc. Natl. Acad. Sci. USA 101 (2004) 12450–12454. [PMID: 15314242]
3.  Schimmel, P. and Beebe, K. Molecular biology: genetic code seizes pyrrolysine. Nature 431 (2004) 257–258. [PMID: 15372017]
[EC 6.1.1.26 created 2007]
 
 
EC 6.1.1.27     
Accepted name: O-phospho-L-serine—tRNA ligase
Reaction: ATP + O-phospho-L-serine + tRNACys = AMP + diphosphate + O-phospho-L-seryl-tRNACys
Other name(s): O-phosphoseryl-tRNA ligase; non-canonical O-phosphoseryl-tRNA synthetase; SepRS
Systematic name: O-phospho-L-serine:tRNACys ligase (AMP-forming)
Comments: In organisms like Archaeoglobus fulgidus lacking EC 6.1.1.16 (cysteine—tRNA ligase) for the direct Cys-tRNACys formation, Cys-tRNACys is produced by an indirect pathway, in which EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) ligates O-phosphoserine to tRNACys, and EC 2.5.1.73 (O-phospho-L-seryl-tRNA: Cys-tRNA synthase) converts the produced O-phospho-L-seryl-tRNACys to Cys-tRNACys. The SepRS/SepCysS pathway is the sole route for cysteine biosynthesis in the organism [1]. Methanosarcina mazei can use both pathways, the direct route using EC 6.1.1.16 (cysteine—tRNA ligase) and the indirect pathway with EC 6.1.1.27 and EC 2.5.1.73 (O-phospho-L-seryl-tRNA: Cys-tRNA synthase) [2].
References:
1.  Fukunaga, R. and Yokoyama, S. Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea. Nat. Struct. Mol. Biol. 14 (2007) 272–279. [PMID: 17351629]
2.  Hauenstein, S.I. and Perona, J.J. Redundant synthesis of cysteinyl-tRNACys in Methanosarcina mazei. J. Biol. Chem. 283 (2008) 22007–22017. [PMID: 18559341]
[EC 6.1.1.27 created 2009]
 
 
EC 6.1.1.28      
Deleted entry: proline/cysteine—tRNA ligase. Later published work having demonstrated that this was not a genuine enzyme, EC 6.1.1.28 was withdrawn at the public-review stage before being made official.
[EC 6.1.1.28 created 2014, deleted 2014]
 
 
EC 6.1.2.1     
Accepted name: D-alanine—(R)-lactate ligase
Reaction: D-alanine + (R)-lactate + ATP = D-alanyl-(R)-lactate + ADP + phosphate
Glossary: (R)-lactate = D-lactate
D-alanyl-(R)-lactate = D-alanyl-D-lactate = (2R)-2-(D-alanyloxy)propanoic acid = (R)-2-((R)-2-aminopropanoyloxy)propanoic acid
Other name(s): VanA; VanB; VanD
Systematic name: D-alanine:(R)-lactate ligase (ADP-forming)
Comments: The product of this enzyme, the depsipeptide D-alanyl-(R)-lactate, can be incorporated into the peptidoglycan pentapeptide instead of the usual D-alanyl-D-alanine dipeptide, which is formed by EC 6.3.2.4, D-alanine—D-alanine ligase. The resulting peptidoglycan does not bind the glycopeptide antibiotics vancomycin and teicoplanin, conferring resistance on the bacteria.
References:
1.  Bugg, T.D., Wright, G.D., Dutka-Malen, S., Arthur, M., Courvalin, P. and Walsh, C.T. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry 30 (1991) 10408–10415. [PMID: 1931965]
2.  Meziane-Cherif, D., Badet-Denisot, M.A., Evers, S., Courvalin, P. and Badet, B. Purification and characterization of the VanB ligase associated with type B vancomycin resistance in Enterococcus faecalis V583. FEBS Lett. 354 (1994) 140–142. [PMID: 7957913]
3.  Perichon, B., Reynolds, P. and Courvalin, P. VanD-type glycopeptide-resistant Enterococcus faecium BM4339. Antimicrob. Agents Chemother. 41 (1997) 2016–2018. [PMID: 9303405]
[EC 6.1.2.1 created 2010]
 
 
EC 6.1.2.2     
Accepted name: nebramycin 5′ synthase
Reaction: (1) tobramycin + carbamoyl phosphate + ATP + H2O = nebramycin 5′ + AMP + diphosphate + phosphate (overall reaction)
(1a) carbamoyl phosphate + ATP + H2O = diphosphate + O-carbamoyladenylate + phosphate
(1b) O-carbamoyladenylate + tobramycin = AMP + nebramycin 5′
(2) kanamycin A + carbamoyl phosphate + ATP + H2O = 6′′-O-carbamoylkanamycin A + AMP + diphosphate + phosphate (overall reaction)
(2a) carbamoyl phosphate + ATP + H2O = diphosphate + O-carbamoyladenylate + phosphate
(2b) O-carbamoyladenylate + kanamycin A = AMP + 6′′-O-carbamoylkanamycin A
Glossary: tobramycin = (1S,2S,3R,4S,6R)-4,6-diamino-3-(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyloxy)-2-hydroxycyclohexyl 3-amino-3-deoxy-α-D-glucopyranoside
nebramycin 5′ = (1S,2S,3R,4S,6R)-4,6-diamino-3-[(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-6-O-carbamoyl-3-deoxy-α-D-glucopyranoside
kanamycin A = (1S,2R,3R,4S,6R)-4,6-diamino-3-(6-amino-6-deoxy--D-glucopyranosyloxy)-2-hydroxycyclohexyl 3-amino-3-deoxy--D-glucopyranoside
6′′-O-carbamoylkanamycin A = (1S,2R,3R,4S,6R)-4,6-diamino-3-[(6-amino-6-deoxy-α-D-glucopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-6-O-carbamoyl-3-deoxy-α-D-glucopyranoside
Other name(s): tobramycin carbamoyltransferase; TobZ
Systematic name: tobramycin:carbamoyl phosphate ligase (AMP,phosphate-forming)
Comments: Requires Fe(III). The enzyme from the bacterium Streptoalloteichus tenebrarius catalyses the activation of carbamoyl phosphate to O-carbamoyladenylate and the subsequent carbamoylation of kanamycin and tobramycin.
References:
1.  Parthier, C., Gorlich, S., Jaenecke, F., Breithaupt, C., Brauer, U., Fandrich, U., Clausnitzer, D., Wehmeier, U.F., Bottcher, C., Scheel, D. and Stubbs, M.T. The O-carbamoyltransferase TobZ catalyzes an ancient enzymatic reaction. Angew. Chem. Int. Ed. Engl. 51 (2012) 4046–4052. [PMID: 22383337]
[EC 6.1.2.2 created 2014]
 
 
EC 6.1.3.1     
Accepted name: olefin β-lactone synthetase
Reaction: ATP + a (2R,3S)-2-alkyl-3-hydroxyalkanoate = AMP + diphosphate + a cis-3-alkyl-4-alkyloxetan-2-one
Other name(s): oleC (gene name)
Systematic name: (2R,3S)-2-alkyl-3-hydroxyalkanoate ligase (β-lactone,AMP-forming)
Comments: The enzyme, found in certain bacterial species, participates in a pathway for the production of olefins. It forms a β-lactone. The alkyl group at C2 of the substrate ends up as the 3-alkyl group of the product.
References:
1.  Sukovich, D.J., Seffernick, J.L., Richman, J.E., Hunt, K.A., Gralnick, J.A. and Wackett, L.P. Structure, function, and insights into the biosynthesis of a head-to-head hydrocarbon in Shewanella oneidensis strain MR-1. Appl. Environ. Microbiol. 76 (2010) 3842–3849. [PMID: 20418444]
2.  Frias, J.A., Goblirsch, B.R., Wackett, L.P. and Wilmot, C.M. Cloning, purification, crystallization and preliminary X-ray diffraction of the OleC protein from Stenotrophomonas maltophilia involved in head-to-head hydrocarbon biosynthesis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66 (2010) 1108–1110. [PMID: 20823539]
3.  Kancharla, P., Bonnett, S.A. and Reynolds, K.A. Stenotrophomonas maltophilia OleC-catalyzed ATP-dependent formation of long-chain Z-olefins from 2-alkyl-3-hydroxyalkanoic acids. Chembiochem 17 (2016) 1426–1429. [PMID: 27238740]
4.  Christenson, J.K., Richman, J.E., Jensen, M.R., Neufeld, J.Y., Wilmot, C.M. and Wackett, L.P. β-Lactone synthetase found in the olefin biosynthesis pathway. Biochemistry 56 (2017) 348–351. [PMID: 28029240]
[EC 6.1.3.1 created 2017]
 
 
EC 6.2.1.1     
Accepted name: acetate—CoA ligase
Reaction: ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
Other name(s): acetyl-CoA synthetase; acetyl activating enzyme; acetate thiokinase; acyl-activating enzyme; acetyl coenzyme A synthetase; acetic thiokinase; acetyl CoA ligase; acetyl CoA synthase; acetyl-coenzyme A synthase; short chain fatty acyl-CoA synthetase; short-chain acyl-coenzyme A synthetase; ACS
Systematic name: acetate:CoA ligase (AMP-forming)
Comments: Also acts on propanoate and propenoate.
References:
1.  Chou, T.C. and Lipmann, F. Separation of acetyl transfer enzymes in pigeon liver extract. J. Biol. Chem. 196 (1952) 89–103. [PMID: 12980945]
2.  Eisenberg, M.A. The acetate-activating enzyme of Rhodospirillum rubrum. Biochim. Biophys. Acta 16 (1955) 58–65. [PMID: 14363230]
3.  Hele, P. The acetate activating enzyme of beef heart. J. Biol. Chem. 206 (1954) 671–676. [PMID: 13143026]
4.  Millerd, A. and Bonner, J. Acetate activation and acetoacetate formation in plant systems. Arch. Biochem. Biophys. 49 (1954) 343–355. [PMID: 13159282]
[EC 6.2.1.1 created 1961]
 
 
EC 6.2.1.2     
Accepted name: butyrate—CoA ligase
Reaction: ATP + a carboxylate + CoA = AMP + diphosphate + an acyl-CoA
Other name(s): butyryl-CoA synthetase; fatty acid thiokinase (medium chain); acyl-activating enzyme; fatty acid elongase; fatty acid activating enzyme; fatty acyl coenzyme A synthetase; medium chain acyl-CoA synthetase; butyryl-coenzyme A synthetase; L-(+)-3-hydroxybutyryl CoA ligase; short-chain acyl-CoA synthetase
Systematic name: butanoate:CoA ligase (AMP-forming)
Comments: Acts on acids from C4 to C11 and on the corresponding 3-hydroxy- and 2,3- or 3,4-unsaturated acids.
References:
1.  Mahler, H.R., Wakil, S.J. and Bock, R.M. Studies on fatty acid oxidation. I. Enzymatic activation of fatty acids. J. Biol. Chem. 204 (1953) 453–468. [PMID: 13084616]
2.  Massaro, E.J. and Lennarz, W.J. The partial purification and characterization of a bacterial fatty acyl coenzyme A synthetase. Biochemistry 4 (1965) 85–90. [PMID: 14285249]
3.  Websterlt, J.R., Gerowin, L.D. and Rakita, L. Purification and characteristics of a butyryl coenzyme A synthetase from bovine heart mitochondria. J. Biol. Chem. 240 (1965) 29–33. [PMID: 14253428]
[EC 6.2.1.2 created 1961, modified 2011]
 
 
EC 6.2.1.3     
Accepted name: long-chain-fatty-acid—CoA ligase
Reaction: ATP + a long-chain fatty acid + CoA = AMP + diphosphate + an acyl-CoA
Glossary: a long-chain-fatty acid = a fatty acid with an aliphatic chain of 13-22 carbons.
Other name(s): acyl-CoA synthetase; fatty acid thiokinase (long chain); acyl-activating enzyme; palmitoyl-CoA synthase; lignoceroyl-CoA synthase; arachidonyl-CoA synthetase; acyl coenzyme A synthetase; acyl-CoA ligase; palmitoyl coenzyme A synthetase; thiokinase; palmitoyl-CoA ligase; acyl-coenzyme A ligase; fatty acid CoA ligase; long-chain fatty acyl coenzyme A synthetase; oleoyl-CoA synthetase; stearoyl-CoA synthetase; long chain fatty acyl-CoA synthetase; long-chain acyl CoA synthetase; fatty acid elongase; LCFA synthetase; pristanoyl-CoA synthetase; ACS3; long-chain acyl-CoA synthetase I; long-chain acyl-CoA synthetase II; fatty acyl-coenzyme A synthetase; long-chain acyl-coenzyme A synthetase; FAA1
Systematic name: long-chain fatty acid:CoA ligase (AMP-forming)
Comments: Acts on a wide range of long-chain saturated and unsaturated fatty acids, but the enzymes from different tissues show some variation in specificity. The liver enzyme acts on acids from C6 to C20; that from brain shows high activity up to C24.
References:
1.  Bakken, A.M. and Farstad, M. Identical subcellular distribution of palmitoyl-CoA and arachidonoyl-CoA synthetase activities in human blood platelets. Biochem. J. 261 (1989) 71–76. [PMID: 2528345]
2.  Hosaka, K., Mishima, M., Tanaka, T., Kamiryo, T. and Numa, S. Acyl-coenzyme-A synthetase I from Candida lipolytica. Purification, properties and immunochemical studies. Eur. J. Biochem. 93 (1979) 197–203. [PMID: 108099]
3.  Nagamatsu, K., Soeda, S., Mori, M. and Kishimoto, Y. Lignoceroyl-coenzyme A synthetase from developing rat brain: partial purification, characterization and comparison with palmitoyl-coenzyme A synthetase activity and liver enzyme. Biochim. Biophys. Acta 836 (1985) 80–88. [PMID: 3161545]
4.  Tanaka, T., Hosaka, K., Hoshimaru, M. and Numa, S. Purification and properties of long-chain acyl-coenzyme-A synthetase from rat liver. Eur. J. Biochem. 98 (1979) 165–172. [PMID: 467438]
[EC 6.2.1.3 created 1961, modified 1989, modified 2011]
 
 
EC 6.2.1.4     
Accepted name: succinate—CoA ligase (GDP-forming)
Reaction: GTP + succinate + CoA = GDP + phosphate + succinyl-CoA
Other name(s): succinyl-CoA synthetase (GDP-forming); succinyl coenzyme A synthetase (guanosine diphosphate-forming); succinate thiokinase; succinic thiokinase; succinyl coenzyme A synthetase; succinate-phosphorylating enzyme; P-enzyme; SCS; G-STK; succinyl coenzyme A synthetase (GDP-forming); succinyl CoA synthetase; succinyl coenzyme A synthetase
Systematic name: succinate:CoA ligase (GDP-forming)
Comments: Itaconate can act instead of succinate, and ITP instead of GTP.
References:
1.  Hager, L.P. Succinyl CoA synthetase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 6, Academic Press, New York, 1962, pp. 387–399.
2.  Kaufman, S., Gilvarg, C., Cori, O. and Ochoa, S. Enzymatic oxidation of α-ketoglutarate and coupled phosphorylation. J. Biol. Chem. 203 (1953) 869–888. [PMID: 13084656]
3.  Mazumder, R., Sanadi, D.R. and Rodwell, W.V. Purification and properties of hog kidney succinic thiokinase. J. Biol. Chem. 235 (1960) 2546–2550. [PMID: 13768680]
4.  Sanadi, D.R., Gibson, D.M. and Ayengar, P. Guanosine triphosphate, the primary product of phosphorylation coupled to the breakdown of succinyl coenzyme A. Biochim. Biophys. Acta 14 (1954) 434–436. [PMID: 13181903]
[EC 6.2.1.4 created 1961]
 
 
EC 6.2.1.5     
Accepted name: succinate—CoA ligase (ADP-forming)
Reaction: ATP + succinate + CoA = ADP + phosphate + succinyl-CoA
Other name(s): succinyl-CoA synthetase (ADP-forming); succinic thiokinase; succinate thiokinase; succinyl-CoA synthetase; succinyl coenzyme A synthetase (adenosine diphosphate-forming); succinyl coenzyme A synthetase; A-STK (adenin nucleotide-linked succinate thiokinase); STK; A-SCS
Systematic name: succinate:CoA ligase (ADP-forming)
References:
1.  Hager, L.P. Succinyl CoA synthetase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 6, Academic Press, New York, 1962, pp. 387–399.
2.  Kaufman, S. Studies on the mechanism of the reaction catalyzed by the phosphorylating enzyme. J. Biol. Chem. 216 (1955) 153–164. [PMID: 13252015]
3.  Kaufman, S. and Alivasatos, S.G.A. Purification and properties of the phosphorylating enzyme from spinach. J. Biol. Chem. 216 (1955) 141–152. [PMID: 13252014]
[EC 6.2.1.5 created 1961]
 
 
EC 6.2.1.6     
Accepted name: glutarate—CoA ligase
Reaction: ATP + glutarate + CoA = ADP + phosphate + glutaryl-CoA
Other name(s): glutaryl-CoA synthetase; glutaryl coenzyme A synthetase
Systematic name: glutarate:CoA ligase (ADP-forming)
Comments: GTP or ITP can act instead of ATP.
References:
1.  Menon, G.K.K., Friedman, D.L. and Stern, J.R. Enzymic synthesis of glutaryl-coenzyme A. Biochim. Biophys. Acta 44 (1960) 375–377. [PMID: 13769477]
[EC 6.2.1.6 created 1961]
 
 
EC 6.2.1.7     
Accepted name: cholate—CoA ligase
Reaction: (1) ATP + cholate + CoA = AMP + diphosphate + choloyl-CoA
(2) ATP + (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + CoA = AMP + diphosphate + (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA
Glossary: cholate = 3α,7α,12α-trihydroxy-5β-cholan-24-oate
trihydroxycoprostanoate = 3α,7α,12α-trihydroxy-5β-cholestan-26-oate
Other name(s): BAL; bile acid CoA ligase; bile acid coenzyme A ligase; choloyl-CoA synthetase; choloyl coenzyme A synthetase; cholic thiokinase; cholate thiokinase; cholic acid:CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanoyl coenzyme A synthetase; 3α,7α,12α-trihydroxy-5β-cholestanoate-CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanoate-CoA synthetase; THCA-CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanate—CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanate:CoA ligase (AMP-forming); cholyl-CoA synthetase; trihydroxycoprostanoyl-CoA synthetase
Systematic name: cholate:CoA ligase (AMP-forming)
Comments: Requires Mg2+ for activity. The mammalian enzyme is membrane-bound and catalyses the first step in the conjugation of bile acids with amino acids, converting bile acids into their acyl-CoA thioesters. Chenodeoxycholate, deoxycholate, lithocholate and trihydroxycoprostanoate can also act as substrates [7]. The bacterial enzyme is soluble and participates in an anaerobic bile acid 7 α-dehydroxylation pathway [5].
References:
1.  Elliott, W.H. The enzymic activation of cholic acid by guinea-pig-liver microsomes. Biochem. J. 62 (1956) 427–433. [PMID: 13303991]
2.  Elliott, W.H. The breakdown of adenosine triphosphate accompanying cholic acid activation by guinea-pig liver microsomes. Biochem. J. 65 (1957) 315–321. [PMID: 13403911]
3.  Prydz, K., Kase, B.F., Björkhem, I. and Pedersen, J.I. Subcellular localization of 3α,7α-dihydroxy- and 3α,7α,12α-trihydroxy-5β-cholestanoyl-coenzyme A ligase(s) in rat liver. J. Lipid Res. 29 (1988) 997–1004. [PMID: 3183523]
4.  Schepers, L., Casteels, M., Verheyden, K., Parmentier, G., Asselberghs, S., Eyssen, H.J. and Mannaerts, G.P. Subcellular distribution and characteristics of trihydroxycoprostanoyl-CoA synthetase in rat liver. Biochem. J. 257 (1989) 221–229. [PMID: 2521999]
5.  Mallonee, D.H., Adams, J.L. and Hylemon, P.B. The bile acid-inducible baiB gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A ligase. J. Bacteriol. 174 (1992) 2065–2071. [PMID: 1551828]
6.  Wheeler, J.B., Shaw, D.R. and Barnes, S. Purification and characterization of a rat liver bile acid coenzyme A ligase from rat liver microsomes. Arch. Biochem. Biophys. 348 (1997) 15–24. [PMID: 9390170]
7.  Falany, C.N., Xie, X., Wheeler, J.B., Wang, J., Smith, M., He, D. and Barnes, S. Molecular cloning and expression of rat liver bile acid CoA ligase. J. Lipid Res. 43 (2002) 2062–2071. [PMID: 12454267]
[EC 6.2.1.7 created 1961 (EC 6.2.1.29 created 1992, incorporated 2005), modified 2005]
 
 
EC 6.2.1.8     
Accepted name: oxalate—CoA ligase
Reaction: ATP + oxalate + CoA = AMP + diphosphate + oxalyl-CoA
Other name(s): oxalyl-CoA synthetase; oxalyl coenzyme A synthetase
Systematic name: oxalate:CoA ligase (AMP-forming)
References:
1.  Giovanelli, J. Oxalyl-coenzyme A synthetase from pea seeds. Biochim. Biophys. Acta 118 (1966) 124–143. [PMID: 4288975]
[EC 6.2.1.8 created 1972]
 
 
EC 6.2.1.9     
Accepted name: malate—CoA ligase
Reaction: ATP + malate + CoA = ADP + phosphate + malyl-CoA
Other name(s): malyl-CoA synthetase; malyl coenzyme A synthetase; malate thiokinase
Systematic name: malate:CoA ligase (ADP-forming)
References:
1.  Mue, S., Tuboi, S. and Kikuchi, G. On malyl-coenzyme A synthetase. J. Biochem. (Tokyo) 56 (1964) 545–551. [PMID: 14244056]
[EC 6.2.1.9 created 1972]
 
 
EC 6.2.1.10     
Accepted name: carboxylic acid—CoA ligase (GDP-forming)
Reaction: GTP + a carboxylate + CoA = GDP + phosphate + acyl-CoA
Other name(s): acyl-CoA synthetase (GDP-forming); acyl coenzyme A synthetase (guanosine diphosphate forming)
Systematic name: carboxylic acid:CoA ligase (GDP-forming)
References:
1.  Rossi, C.R. and Gibson, D.M. Activation of fatty acids by a guanosine triphosphate-specific thiokinase from liver mitochondria. J. Biol. Chem. 239 (1964) 1694–1699. [PMID: 14213337]
[EC 6.2.1.10 created 1972, modified 2011]
 
 
EC 6.2.1.11     
Accepted name: biotin—CoA ligase
Reaction: ATP + biotin + CoA = AMP + diphosphate + biotinyl-CoA
Other name(s): biotinyl-CoA synthetase; biotin CoA synthetase; biotinyl coenzyme A synthetase
Systematic name: biotin:CoA ligase (AMP-forming)
References:
1.  Christner, J.E., Schlesinger, M.J. and Coon, M.J. Enzymatic activation of biotin. Biotinyl adenylate formation. J. Biol. Chem. 239 (1964) 3997–4005. [PMID: 14257635]
[EC 6.2.1.11 created 1972]
 
 
EC 6.2.1.12     
Accepted name: 4-coumarate—CoA ligase
Reaction: ATP + 4-coumarate + CoA = AMP + diphosphate + 4-coumaroyl-CoA
Glossary: 4-coumarate = 3-(4-hydroxyphenyl)prop-2-enoate
Other name(s): 4-coumaroyl-CoA synthetase; p-coumaroyl CoA ligase; p-coumaryl coenzyme A synthetase; p-coumaryl-CoA synthetase; p-coumaryl-CoA ligase; feruloyl CoA ligase; hydroxycinnamoyl CoA synthetase; 4-coumarate:coenzyme A ligase; caffeolyl coenzyme A synthetase; p-hydroxycinnamoyl coenzyme A synthetase; feruloyl coenzyme A synthetase; sinapoyl coenzyme A synthetase; 4-coumaryl-CoA synthetase; hydroxycinnamate:CoA ligase; p-coumaryl-CoA ligase; p-hydroxycinnamic acid:CoA ligase; 4CL
Systematic name: 4-coumarate:CoA ligase (AMP-forming)
References:
1.  Gross, G.G. and Zenk, M.H. Isolation and properties of hydroxycinnamate: CoA ligase from lignifying tissue of Forsythia. Eur. J. Biochem. 42 (1974) 453–459. [PMID: 4364250]
2.  Lindl, T., Kreuzaler, F. and Hahlbrock, F. Synthesis of p-coumaroyl coenzyme A with a partially purified p-coumarate:CoA ligase from cell suspension cultures of soybean (Glycine max). Biochim. Biophys. Acta 302 (1973) 457–464. [PMID: 4699252]
[EC 6.2.1.12 created 1976]
 
 
EC 6.2.1.13     
Accepted name: acetate—CoA ligase (ADP-forming)
Reaction: ATP + acetate + CoA = ADP + phosphate + acetyl-CoA
Other name(s): acetyl-CoA synthetase (ADP-forming); acetyl coenzyme A synthetase (adenosine diphosphate-forming); acetate thiokinase
Systematic name: acetate:CoA ligase (ADP-forming)
Comments: Also acts on propanoate and, very slowly, on butanoate.
References:
1.  Reeves, R.E., Warren, L.G., Susskind, B. and Lo, H.-S. An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase. J. Biol. Chem. 252 (1977) 726–731. [PMID: 13076]
[EC 6.2.1.13 created 1978]
 
 
EC 6.2.1.14     
Accepted name: 6-carboxyhexanoate—CoA ligase
Reaction: ATP + 6-carboxyhexanoate + CoA = AMP + diphosphate + 6-carboxyhexanoyl-CoA
Other name(s): 6-carboxyhexanoyl-CoA synthetase; pimelyl-CoA synthetase
Systematic name: 6-carboxyhexanoate:CoA ligase (AMP-forming)
References:
1.  Izumi, Y., Morita, H., Sato, K., Tani, Y. and Ogata, K. Synthesis of biotin-vitamers from pimelic acid and coenzyme A by cell-free extracts of various bacteria. Biochim. Biophys. Acta 264 (1972) 210–213. [PMID: 4623286]
2.  Izumi, Y., Morita, H., Tani, Y. and Ogata, K. The pimelyl-CoA synthetase responsible for the first step in biotin biosynthesis by microorganisms. Agric. Biol. Chem. 38 (1974) 2257–2262.
[EC 6.2.1.14 created 1983]
 
 
EC 6.2.1.15     
Accepted name: arachidonate—CoA ligase
Reaction: ATP + arachidonate + CoA = AMP + diphosphate + arachidonoyl-CoA
Glossary: arachidonate = (all-Z)-icosa-5,8,11,14-tetraenoate
Other name(s): arachidonoyl-CoA synthetase
Systematic name: arachidonate:CoA ligase (AMP-forming)
Comments: Not identical with EC 6.2.1.3 long-chain-fatty-acid—CoA ligase. Icosa-8,11,14-trienoate, but not the other long-chain fatty acids, can act in place of arachidonate.
References:
1.  Wilson, D.B., Prescott, S.M. and Majerus, P.W. Discovery of an arachidonoyl coenzyme A synthetase in human platelets. J. Biol. Chem. 257 (1982) 3510–3515. [PMID: 7061494]
[EC 6.2.1.15 created 1984]
 
 
EC 6.2.1.16     
Accepted name: acetoacetate—CoA ligase
Reaction: ATP + acetoacetate + CoA = AMP + diphosphate + acetoacetyl-CoA
Other name(s): acetoacetyl-CoA synthetase
Systematic name: acetoacetate:CoA ligase (AMP-forming)
Comments: Also acts, more slowly, on L-3-hydroxybutanoate.
References:
1.  Fukui, T., Ito, M. and Tomita, K. Purification and characterization of acetoacetyl-CoA synthetase from Zoogloea ramigera I-16-M. Eur. J. Biochem. 127 (1982) 423–428. [PMID: 7140777]
[EC 6.2.1.16 created 1984]
 
 
EC 6.2.1.17     
Accepted name: propionate—CoA ligase
Reaction: ATP + propanoate + CoA = AMP + diphosphate + propanoyl-CoA
Other name(s): propionyl-CoA synthetase
Systematic name: propanoate:CoA ligase (AMP-forming)
Comments: Propenoate can act instead of propanoate. Not identical with EC 6.2.1.1 (acetate—CoA ligase) or EC 6.2.1.2 (butyrate—CoA ligase).
References:
1.  Ricks, C.A. and Cook, R.M. Regulation of volatile fatty acid uptake by mitochondrial acyl CoA synthetases of bovine liver. J. Dairy Sci. 64 (1981) 2324–2335. [PMID: 7341659]
[EC 6.2.1.17 created 1984]
 
 
EC 6.2.1.18     
Accepted name: citrate—CoA ligase
Reaction: ATP + citrate + CoA = ADP + phosphate + (3S)-citryl-CoA
Glossary: citrate = 2-hydroxypropane-1,2,3-tricarboxylate
Other name(s): citryl-CoA synthetase; citrate:CoA ligase; citrate thiokinase
Systematic name: citrate:CoA ligase (ADP-forming)
Comments: The enzyme is a component of EC 2.3.3.8 ATP citrate synthase.
References:
1.  Lill, U., Schreil, A. and Eggerer, H. Isolation of enzymically active fragments formed by limited proteolysis of ATP citrate lyase. Eur. J. Biochem. 125 (1982) 645–650. [PMID: 6749502]
2.  Aoshima, M., Ishii, M. and Igarashi, Y. A novel enzyme, citryl-CoA synthetase, catalysing the first step of the citrate cleavage reaction in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 52 (2004) 751–761. [PMID: 15101981]
[EC 6.2.1.18 created 1986]
 
 
EC 6.2.1.19     
Accepted name: long-chain-fatty-acid—protein ligase
Reaction: ATP + a long-chain fatty acid + [protein]-L-cysteine = AMP + diphosphate + a [protein]-S-(long-chain-acyl)-L-cysteine
Other name(s): luxE (gene name); acyl-protein synthetase; long-chain-fatty-acid—luciferin-component ligase
Systematic name: long-chain-fatty-acid:protein ligase (AMP-forming)
Comments: Together with a hydrolase component (EC 3.1.2.2/EC 3.1.2.14) and a reductase component (EC 1.2.1.50), this enzyme forms a multienzyme fatty acid reductase complex that produces the long-chain aldehyde substrate of the bacterial luciferase enzyme (EC 1.14.14.3). The enzyme activates free long-chain fatty acids, generated by the action of the transferase component, forming a fatty acyl-AMP intermediate, followed by the transfer of the acyl group to an internal L-cysteine residue. It then transfers the acyl group to EC 1.2.1.50, long-chain acyl-protein thioester reductase.
References:
1.  Riendeau, D., Rodrigues, A. and Meighen, E. Resolution of the fatty acid reductase from Photobacterium phosphoreum into acyl protein synthetase and acyl-CoA reductase activities. Evidence for an enzyme complex. J. Biol. Chem. 257 (1982) 6908–6915. [PMID: 7085612]
2.  Rodriguez, A. and Meighen, E. Fatty acyl-AMP as an intermediate in fatty acid reduction to aldehyde in luminescent bacteria. J. Biol. Chem. 260 (1985) 771–774. [PMID: 3968067]
3.  Wall, L. and Meighen, E.A. Subunit structure of the fatty-acid reductase complex from Photobacterium phosphoreum. Biochemistry 25 (1986) 4315–4321.
4.  Soly, R.R. and Meighen, E.A. Identification of the acyl transfer site of fatty acyl-protein synthetase from bioluminescent bacteria. J. Mol. Biol. 219 (1991) 69–77. [PMID: 2023262]
5.  Lin, J.W., Chao, Y.F. and Weng, S.F. Nucleotide sequence and functional analysis of the luxE gene encoding acyl-protein synthetase of the lux operon from Photobacterium leiognathi. Biochem. Biophys. Res. Commun. 228 (1996) 764–773. [PMID: 8941351]
[EC 6.2.1.19 created 1986, modified 2011, modified 2016]
 
 
EC 6.2.1.20     
Accepted name: long-chain-fatty-acid—[acyl-carrier-protein] ligase
Reaction: ATP + a long-chain fatty acid + an [acyl-carrier protein] = AMP + diphosphate + a long-chain acyl-[acyl-carrier protein]
Other name(s): acyl-[acyl-carrier-protein] synthetase (ambiguous); acyl-ACP synthetase (ambiguous); stearoyl-ACP synthetase; acyl-acyl carrier protein synthetase (ambiguous); long-chain-fatty-acid:[acyl-carrier-protein] ligase (AMP-forming)
Systematic name: long-chain-fatty-acid:[acyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme ligates long chain fatty acids (with aliphatic chain of 13-22 carbons) to an acyl-carrier protein. Not identical with EC 6.2.1.3 long-chain-fatty-acid—CoA ligase.
References:
1.  Ray, T.K. and Cronan, J.E., Jr. Activation of long chain fatty acids with acyl carrier protein: demonstration of a new enzyme, acyl-acyl carrier protein synthetase, in Escherichia coli. Proc. Natl. Acad. Sci. USA 73 (1976) 4374–4378. [PMID: 794875]
2.  Kaczmarzyk, D. and Fulda, M. Fatty acid activation in cyanobacteria mediated by acyl-acyl carrier protein synthetase enables fatty acid recycling. Plant Physiol. 152 (2010) 1598–1610. [PMID: 20061450]
[EC 6.2.1.20 created 1986]
 
 
EC 6.2.1.21      
Deleted entry:  phenylacetate—CoA ligase. Activity covered by EC 6.2.1.30, phenylacetate—CoA ligase
[EC 6.2.1.21 created 1986, deleted 2001]
 
 
EC 6.2.1.22     
Accepted name: [citrate (pro-3S)-lyase] ligase
Reaction: ATP + acetate + holo-[citrate (pro-3S)-lyase] = AMP + diphosphate + acetyl-[citrate (pro-3S)-lyase]
Glossary: citrate = 2-hydroxypropane-1,2,3-tricarboxylate
Other name(s): citrate lyase ligase; citrate lyase synthetase; acetate: SH-[acyl-carrier-protein] enzyme ligase (AMP); acetate:HS-citrate lyase ligase; acetate:citrate-(pro-3S)-lyase(thiol-form) ligase (AMP-forming); acetate:[citrate-(pro-3S)-lyase](thiol-form) ligase (AMP-forming)
Systematic name: acetate:holo-[citrate-(pro-3S)-lyase] ligase (AMP-forming)
Comments: Both this enzyme and EC 2.3.1.49,deacetyl-[citrate-(pro-3S)-lyase] S-acetyltransferase, acetylate and activate EC 4.1.3.6, citrate (pro-3S)-lyase.
References:
1.  Antranikian, G. and Gottschalk, G. Copurification of citrate lyase and citrate lyase ligase from Rhodopseudomonas gelatinosa and subsequent separation of the two enzymes. Eur. J. Biochem. 126 (1982) 43–47. [PMID: 7128585]
2.  Antranikian, G., Herzberg, C. and Gottschalk, G. Covalent modification of citrate lyase ligase from Clostridium sphenoides by phosphorylation/dephosphorylation. Eur. J. Biochem. 153 (1985) 413–420. [PMID: 3935436]
3.  Quentmeier, A. and Antranikian, G. Characterization of citrate lyase from Clostridium sporosphaeroides. Arch. Microbiol. 141 (1985) 85–90. [PMID: 3994485]
4.  Schmellenkamp, H. and Eggerer, H. Mechanism of enzymic acetylation of des-acetyl citrate lyase. Proc. Natl. Acad. Sci. USA 71 (1974) 1987–1991. [PMID: 4365579]
[EC 6.2.1.22 created 1989]
 
 
EC 6.2.1.23     
Accepted name: dicarboxylate—CoA ligase
Reaction: ATP + an α,ω-dicarboxylate + CoA = AMP + diphosphate + an ω-carboxyacyl-CoA
Other name(s): carboxylyl-CoA synthetase; dicarboxylyl-CoA synthetase
Systematic name: ω-dicarboxylate:CoA ligase (AMP-forming)
Comments: Acts on dicarboxylic acids of chain length C5 to C16; the best substrate is dodecanedioic acid.
References:
1.  Vamecq, J., de Hoffmann, E. and van Hoof, F. The microsomal dicarboxylyl-CoA synthetase. Biochem. J. 230 (1985) 683–693. [PMID: 4062873]
[EC 6.2.1.23 created 1989, modified 2011]
 
 
EC 6.2.1.24     
Accepted name: phytanate—CoA ligase
Reaction: ATP + phytanate + CoA = AMP + diphosphate + phytanoyl-CoA
Other name(s): phytanoyl-CoA ligase
Systematic name: phytanate:CoA ligase (AMP-forming)
Comments: Not identical with EC 6.2.1.20 long-chain-fatty-acid—[acyl-carrier-protein] ligase.
References:
1.  Muralidharan, F.N. and Muralidharan, V.B. Phytanoyl-CoA ligase activity in rat liver. Biochem. Int. 13 (1986) 123–130. [PMID: 3753503]
[EC 6.2.1.24 created 1989]
 
 
EC 6.2.1.25     
Accepted name: benzoate—CoA ligase
Reaction: ATP + benzoate + CoA = AMP + diphosphate + benzoyl-CoA
Other name(s): benzoate—coenzyme A ligase; benzoyl-coenzyme A synthetase; benzoyl CoA synthetase (AMP forming)
Systematic name: benzoate:CoA ligase (AMP-forming)
Comments: Also acts on 2-, 3- and 4-fluorobenzoate, but only very slowly on the corresponding chlorobenzoates.
References:
1.  Hutber, G.N. and Ribbons, D.W. Involvement of coenzyme-A esters in the metabolism of benzoate and cyclohexanecarboxylate by Rhodopseudomonas palustris. J. Gen. Microbiol. 129 (1983) 2413–2420.
2.  Schennen, U., Braun, K. and Knackmuss, H.-J. Anaerobic degradation of 2-fluorobenzoate by benzoate-degrading, denitrifying bacteria. J. Bacteriol. 161 (1985) 321–325. [PMID: 2857161]
[EC 6.2.1.25 created 1989]
 
 
EC 6.2.1.26     
Accepted name: o-succinylbenzoate—CoA ligase
Reaction: ATP + 2-succinylbenzoate + CoA = AMP + diphosphate + 4-(2-carboxyphenyl)-4-oxobutanoyl-CoA
Glossary: 2-succinylbenzoate = o-succinylbenzoate = 4-(2-carboxyphenyl)-4-oxobutanoate
Other name(s): o-succinylbenzoyl-coenzyme A synthetase; o-succinylbenzoate:CoA ligase (AMP-forming)
Systematic name: 2-succinylbenzoate:CoA ligase (AMP-forming)
References:
1.  Heide, L., Arendt, S. and Leistner, E. Enzymatic-synthesis, characterization, and metabolism of the coenzyme-A ester of o-succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis. J. Biol. Chem. 257 (1982) 7396–7400. [PMID: 7045104]
2.  Kolkmann, R. and Leistner, E. 4-(2′-Carboxyphenyl)-4-oxobutyryl coenzyme A ester, an intermediate in vitamin K2 (menaquinone) biosynthesis. Z. Naturforsch. C: Sci. 42 (1987) 1207–1214. [PMID: 2966501]
3.  Meganathan, R. and Bentley, R. Menaquinone (vitamin K2) biosynthesis: conversion of o-succinylbenzoic acid to 1,4-dihydroxy-2-naphthoic acid by Mycobacterium phlei enzymes. J. Bacteriol. 140 (1979) 92–98. [PMID: 500558]
[EC 6.2.1.26 created 1992]
 
 
EC 6.2.1.27     
Accepted name: 4-hydroxybenzoate—CoA ligase
Reaction: ATP + 4-hydroxybenzoate + CoA = AMP + diphosphate + 4-hydroxybenzoyl-CoA
Other name(s): 4-hydroxybenzoate-CoA synthetase; 4-hydroxybenzoate—coenzyme A ligase (AMP-forming); 4-hydroxybenzoyl coenzyme A synthetase; 4-hydroxybenzoyl-CoA ligase
Systematic name: 4-hydroxybenzoate:CoA ligase (AMP-forming)
References:
1.  Merkel, S.M., Eberhard, A.E., Gibson, J. and Harwood, C.S. Involvement of coenzyme A thioesters in anaerobic metabolism of 4-hydroxybenzoate by Rhodopseudomonas palustris. J. Bacteriol. 171 (1989) 1–7. [PMID: 2914844]
[EC 6.2.1.27 created 1992]
 
 
EC 6.2.1.28     
Accepted name: 3α,7α-dihydroxy-5β-cholestanate—CoA ligase
Reaction: ATP + (25R)-3α,7α-dihydroxy-5β-cholestan-26-oate + CoA = AMP + diphosphate + (25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA
Other name(s): 3α,7α-dihydroxy-5β-cholestanoyl coenzyme A synthetase; DHCA-CoA ligase; 3α,7α-dihydroxy-5β-cholestanate:CoA ligase (AMP-forming)
Systematic name: (25R)-3α,7α-dihydroxy-5β-cholestan-26-oate:CoA ligase (AMP-forming)
References:
1.  Prydz, K., Kase, B.F., Björkhem, I. and Pedersen, J.I. Subcellular localization of 3α,7α-dihydroxy- and 3α,7α,12α-trihydroxy-5β-cholestanoyl-coenzyme A ligase(s) in rat liver. J. Lipid Res. 29 (1988) 997–1004. [PMID: 3183523]
[EC 6.2.1.28 created 1992]
 
 
EC 6.2.1.29      
Deleted entry:  3α,7α,12α-trihydroxy-5β-cholestanate—CoA ligase. The enzyme is identical to EC 6.2.1.7, cholate—CoA ligase
[EC 6.2.1.29 created 1992, deleted 2005]
 
 
EC 6.2.1.30     
Accepted name: phenylacetate—CoA ligase
Reaction: ATP + phenylacetate + CoA = AMP + diphosphate + phenylacetyl-CoA
Other name(s): phenacyl coenzyme A synthetase; phenylacetyl-CoA ligase; PA-CoA ligase; phenylacetyl-CoA ligase (AMP-forming)
Systematic name: phenylacetate:CoA ligase (AMP-forming)
Comments: Also acts, more slowly, on acetate, propanoate and butanoate, but not on hydroxy derivatives of phenylacetate and related compounds.
References:
1.  Martinez-Blanco, H., Reglero, A., Rodriguez-Asparicio, L.B. and Luengo, J.M. Purification and biochemical characterization of phenylacetyl-CoA ligase from Pseudomonas putida. A specific enzyme for the catabolism of phenylacetic acid. J. Biol. Chem. 265 (1990) 7084–7090. [PMID: 2324116]
[EC 6.2.1.30 created 1992 (EC 6.2.1.21 created 1986, incorporated 2001)]
 
 
EC 6.2.1.31     
Accepted name: 2-furoate—CoA ligase
Reaction: ATP + 2-furoate + CoA = AMP + diphosphate + 2-furoyl-CoA
Other name(s): 2-furoyl coenzyme A synthetase
Systematic name: 2-furoate:CoA ligase (AMP-forming)
References:
1.  Koenig, K. and Andreesen, J.R. Molybdenum involvement in aerobic degradation of 2-furoic acid by Pseudomonas putida FU1. Appl. Environ. Microbiol. 55 (1989) 1829–1834. [PMID: 16347977]
[EC 6.2.1.31 created 1992]
 
 
EC 6.2.1.32     
Accepted name: anthranilate—CoA ligase
Reaction: ATP + anthranilate + CoA = AMP + diphosphate + anthraniloyl-CoA
Glossary: anthraniloyl-CoA = 2-aminobenzoyl-CoA
Other name(s): anthraniloyl coenzyme A synthetase; 2-aminobenzoate—CoA ligase; 2-aminobenzoate—coenzyme A ligase; 2-aminobenzoate coenzyme A ligase
Systematic name: anthranilate:CoA ligase (AMP-forming)
References:
1.  Altenschmidt, U., Eckerskorn, C. and Fuchs, G. Evidence that enzymes of a novel aerobic 2-amino-benzoate metabolism in denitrifying Pseudomonas are coded on a small plasmid. Eur. J. Biochem. 194 (1990) 647–653. [PMID: 2176602]
[EC 6.2.1.32 created 1992]
 
 
EC 6.2.1.33     
Accepted name: 4-chlorobenzoate—CoA ligase
Reaction: 4-chlorobenzoate + CoA + ATP = 4-chlorobenzoyl-CoA + AMP + diphosphate
Systematic name: 4-chlorobenzoate:CoA ligase
Comments: Requires Mg2+. This enzyme is part of the bacterial 2,4-dichlorobenzoate degradation pathway.
References:
1.  Dunaway-Mariano, D., Babbitt, P.C. On the origins and functions of the enzymes of the 4-chlorobenzoate to 4-hydroxybenzoate converting pathway. Biodegradation 5 (1994) 259–276. [PMID: 7765837]
2.  Loffler, F., Muller, R., Lingens, F. Purification and properties of 4-halobenzoate-coenzyme A ligase from Pseudomonas sp. CBS3. Biol. Chem. Hoppe-Seyler 373 (1992) 1001–1007. [PMID: 1418673]
3.  Chang, K.H., Liang, P.H., Beck, W., Scholten, J.D., Dunaway-Mariano, D. Isolation and characterization of the three polypeptide components of 4-chlorobenzoate dehalogenase from Pseudomonas sp. strain CBS-3. Biochemistry 31 (1992) 5605–5610. [PMID: 1610806]
[EC 6.2.1.33 created 1999]
 
 
EC 6.2.1.34     
Accepted name: trans-feruloyl-CoA synthase
Reaction: ferulic acid + CoA + ATP = feruloyl-CoA + products of ATP breakdown
Other name(s): trans-feruloyl-CoA synthetase; trans-ferulate:CoASH ligase (ATP-hydrolysing); ferulate:CoASH ligase (ATP-hydrolysing)
Systematic name: ferulate:CoA ligase (ATP-hydrolysing)
Comments: Requires Mg2+. It has not yet been established whether AMP + diphosphate or ADP + phosphate are formed in this reaction.
References:
1.  Narbad, A. and Gasson, M.J. Metabolism of ferulic acid via vanillin using a novel CoA-dependent pathway in a newly-isolated strain of Pseudomonas fluorescens. Microbiology 144 (1998) 1397–1405. [PMID: 9611814]
2.  Pometto, A.L. and Crawford, D.L. Whole-cell bioconversion of vanillin to vanillic acid by Streptomyces viridosporus. Appl. Environ. Microbiol. 45 (1983) 1582–1585. [PMID: 6870241]
[EC 6.2.1.34 created 2000]
 
 
EC 6.2.1.35     
Accepted name: acetate—[acyl-carrier protein] ligase
Reaction: ATP + acetate + an [acyl-carrier protein] = AMP + diphosphate + an acetyl-[acyl-carrier protein]
Other name(s): HS-acyl-carrier protein:acetate ligase; [acyl-carrier protein]:acetate ligase; MadH; ACP-SH:acetate ligase
Systematic name: acetate:[acyl-carrier-protein] ligase (AMP-forming)
Comments: This enzyme, from the anaerobic bacterium Malonomonas rubra, is a component of the multienzyme complex EC 4.1.1.89, biotin-dependent malonate decarboxylase. The enzyme uses the energy from hydrolysis of ATP to convert the thiol group of the acyl-carrier-protein-bound 2′-(5-phosphoribosyl)-3′-dephospho-CoA prosthetic group into its acetyl thioester [2].
References:
1.  Hilbi, H., Dehning, I., Schink, B. and Dimroth, P. Malonate decarboxylase of Malonomonas rubra, a novel type of biotin-containing acetyl enzyme. Eur. J. Biochem. 207 (1992) 117–123. [PMID: 1628643]
2.  Berg, M., Hilbi, H. and Dimroth, P. The acyl carrier protein of malonate decarboxylase of Malonomonas rubra contains 2′-(5"-phosphoribosyl)-3′-dephosphocoenzyme A as a prosthetic group. Biochemistry 35 (1996) 4689–4696. [PMID: 8664258]
3.  Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103–115. [PMID: 9128730]
4.  Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3–10. [PMID: 11902724]
[EC 6.2.1.35 created 2008]
 
 
EC 6.2.1.36     
Accepted name: 3-hydroxypropionyl-CoA synthase
Reaction: 3-hydroxypropanoate + ATP + CoA = 3-hydroxypropanoyl-CoA + AMP + diphosphate
Glossary: 3-hydroxypropionyl-CoA = 3-hydroxypropanoyl-CoA
Other name(s): 3-hydroxypropionyl-CoA synthetase (AMP-forming); 3-hydroxypropionate—CoA ligase
Systematic name: hydroxypropanoate:CoA ligase (AMP-forming)
Comments: Catalyses a step in the 3-hydroxypropanoate/4-hydroxybutanoate cycle, an autotrophic CO2 fixation pathway found in some thermoacidophilic archaea [1,2].The enzymes from Metallosphaera sedula and Sulfolobus tokodaii can also use propionate, acrylate, acetate, and butanoate as substrates [2], and are thus different from EC 6.2.1.17 (propionate—CoA ligase), which does not accept acetate or butanoate.
References:
1.  Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782–1786. [PMID: 18079405]
2.  Alber, B.E., Kung, J.W. and Fuchs, G. 3-Hydroxypropionyl-coenzyme A synthetase from Metallosphaera sedula, an enzyme involved in autotrophic CO2 fixation. J. Bacteriol. 190 (2008) 1383–1389. [PMID: 18165310]
[EC 6.2.1.36 created 2009]
 
 
EC 6.2.1.37     
Accepted name: 3-hydroxybenzoate—CoA ligase
Reaction: ATP + 3-hydroxybenzoate + CoA = AMP + diphosphate + 3-hydroxybenzoyl-CoA
Other name(s): 3-hydroxybenzoyl-CoA synthetase; 3-hydroxybenzoate—coenzyme A ligase (AMP-forming); 3-hydroxybenzoyl coenzyme A synthetase; 3-hydroxybenzoyl-CoA ligase
Systematic name: 3-hydroxybenzoate:CoA ligase (AMP-forming)
Comments: The enzyme works equally well with 4-hydroxybenzoate but shows low activity towards benzoate, 4-aminobenzoate, 3-aminobenzoate, 3-fluorobenzoate, 4-fluorobenzoate, 3-chlorobenzoate, and 4-chlorobenzoate. There is no activity with 3,4-dihydroxybenzoate, 2,3-dihydroxybenzoate, and 2-hydroxybenzoate as substrates.
References:
1.  Laempe, D., Jahn, M., Breese, K., Schägger, H. and Fuchs, G. Anaerobic metabolism of 3-hydroxybenzoate by the denitrifying bacterium Thauera aromatica. J. Bacteriol. 183 (2001) 968–979. [PMID: 11208796]
[EC 6.2.1.37 created 2011]
 
 
EC 6.2.1.38     
Accepted name: (2,2,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA synthase
Reaction: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate + ATP + CoA = AMP + diphosphate + [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetyl-CoA
Other name(s): 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-CoA synthetase
Systematic name: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate:CoA ligase (AMP-forming)
Comments: Isolated from Pseudomonas putida. Forms part of the pathway of camphor catabolism.
References:
1.  Ougham, H.J., Taylor, D.G. and Trudgill, P.W. Camphor revisited: involvement of a unique monooxygenase in metabolism of 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetic acid by Pseudomonas putida. J. Bacteriol. 153 (1983) 140–152. [PMID: 6848481]
[EC 6.2.1.38 created 2012]
 
 
EC 6.2.1.39     
Accepted name: [butirosin acyl-carrier protein]—L-glutamate ligase
Reaction: (1) ATP + L-glutamate + BtrI acyl-carrier protein = ADP + phosphate + L-glutamyl-[BtrI acyl-carrier protein]
(2) ATP + L-glutamate + 4-amino butanoyl-[BtrI acyl-carrier protein] = ADP + phosphate + 4-(γ-L-glutamylamino)butanoyl-[BtrI acyl-carrier protein]
Other name(s): [BtrI acyl-carrier protein]—L-glutamate ligase; BtrJ
Systematic name: [BtrI acyl-carrier protein]:L-glutamate ligase (ADP-forming)
Comments: Catalyses two steps in the biosynthesis of the side chain of the aminoglycoside antibiotics of the butirosin family. The enzyme adds one molecule of L-glutamate to a dedicated acyl-carrier protein, and following decarboxylation of the product by EC 4.1.1.95, L-glutamyl-[BtrI acyl-carrier protein] decarboxylase, adds a second L-glutamate molecule. Requires Mg2+ or Mn2+, and activity is enhanced in the presence of Mn2+.
References:
1.  Li, Y., Llewellyn, N.M., Giri, R., Huang, F. and Spencer, J.B. Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway. Chem. Biol. 12 (2005) 665–675. [PMID: 15975512]
[EC 6.2.1.39 created 2012]
 
 
EC 6.2.1.40     
Accepted name: 4-hydroxybutyrate—CoA ligase
Reaction: ATP + 4-hydroxybutanoate + CoA = AMP + diphosphate + 4-hydroxybutanoyl-CoA
Other name(s): 4-hydroxybutyrate-CoA synthetase; 4-hydroxybutyrate:CoA ligase (AMP-forming)
Systematic name: 4-hydroxybutanoate:CoA ligase (AMP-forming)
Comments: Isolated from the archaeon Metallosphaera sedula. Involved in the 3-hydroxypropanoate/4-hydroxybutanoate cycle.
References:
1.  Ramos-Vera, W.H., Weiss, M., Strittmatter, E., Kockelkorn, D. and Fuchs, G. Identification of missing genes and enzymes for autotrophic carbon fixation in crenarchaeota. J. Bacteriol. 193 (2011) 1201–1211. [PMID: 21169482]
2.  Hawkins, A.S., Han, Y., Bennett, R.K., Adams, M.W. and Kelly, R.M. Role of 4-hydroxybutyrate-CoA synthetase in the CO2 fixation cycle in thermoacidophilic archaea. J. Biol. Chem. 288 (2013) 4012–4022. [PMID: 23258541]
[EC 6.2.1.40 created 2014]
 
 
EC 6.2.1.41     
Accepted name: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate—CoA ligase
Reaction: ATP + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate + CoA = AMP + diphosphate + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoyl-CoA
Glossary: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate = HIP
Other name(s): fadD3 (gene name); HIP—CoA ligase
Systematic name: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol and cholate. The enzyme is very specific for its substrate, and requires that the side chain at C17 is completely removed.
References:
1.  Horinouchi, M., Hayashi, T., Koshino, H. and Kudo, T. ORF18-disrupted mutant of Comamonas testosteroni TA441 accumulates significant amounts of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid and its derivatives after incubation with steroids. J. Steroid Biochem. Mol. Biol. 101 (2006) 78–84. [PMID: 16891113]
2.  Casabon, I., Crowe, A.M., Liu, J. and Eltis, L.D. FadD3 is an acyl-CoA synthetase that initiates catabolism of cholesterol rings C and D in actinobacteria. Mol. Microbiol. 87 (2013) 269–283. [PMID: 23146019]
[EC 6.2.1.41 created 2014]
 
 
EC 6.2.1.42     
Accepted name: 3-oxocholest-4-en-26-oate—CoA ligase
Reaction: ATP + (25S)-3-oxocholest-4-en-26-oate + CoA = AMP + diphosphate + (25S)-3-oxocholest-4-en-26-oyl-CoA
Other name(s): fadD19 (gene name)
Systematic name: (25S)-3-oxocholest-4-en-26-oate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol. It is responsible for the activation of the C8 side chain. 3β-hydroxycholest-5-en-26-oate can also be used as substrate.
References:
1.  Wilbrink, M.H., Petrusma, M., Dijkhuizen, L. and van der Geize, R. FadD19 of Rhodococcus rhodochrous DSM43269, a steroid-coenzyme A ligase essential for degradation of C-24 branched sterol side chains. Appl. Environ. Microbiol. 77 (2011) 4455–4464. [PMID: 21602385]
2.  Casabon, I., Swain, K., Crowe, A.M., Eltis, L.D. and Mohn, W.W. Actinobacterial acyl coenzyme a synthetases involved in steroid side-chain catabolism. J. Bacteriol. 196 (2014) 579–587. [PMID: 24244004]
[EC 6.2.1.42 created 2014]
 
 
EC 6.2.1.43     
Accepted name: 2-hydroxy-7-methoxy-5-methyl-1-naphthoate—CoA ligase
Reaction: ATP + 2-hydroxy-7-methoxy-5-methyl-1-naphthoate + CoA = AMP + diphosphate + 2-hydroxy-7-methoxy-5-methyl-1-naphthoyl-CoA
Other name(s): NcsB2
Systematic name: 2-hydroxy-7-methoxy-5-methyl-1-naphthoate:CoA ligase
Comments: The enzyme from the bacterium Streptomyces carzinostaticus is involved in the attachment of the 2-hydroxy-7-methoxy-5-methyl-1-naphthoate moiety of the antibiotic neocarzinostatin. In vitro the enzyme also catalyses the activation of other 1-naphthoic acid analogues, e.g. 2-hydroxy-5-methyl-1-naphthoate or 2,7-dihydroxy-5-methyl-1-naphthoate.
References:
1.  Cooke, H.A., Zhang, J., Griffin, M.A., Nonaka, K., Van Lanen, S.G., Shen, B. and Bruner, S.D. Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase integral to the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J. Am. Chem. Soc. 129 (2007) 7728–7729. [PMID: 17539640]
[EC 6.2.1.43 created 2014]
 
 
EC 6.2.1.44     
Accepted name: 3-(methylthio)propionyl—CoA ligase
Reaction: ATP + 3-(methylsulfanyl)propanoate + CoA = AMP + diphosphate + 3-(methylsulfanyl)propanoyl-CoA
Other name(s): DmdB; MMPA-CoA ligase; methylmercaptopropionate-coenzyme A ligase; 3-methylmercaptopropionyl-CoA ligase; 3-(methylthio)propanoate:CoA ligase (AMP-forming)
Systematic name: 3-(methylsulfanyl)propanoate:CoA ligase (AMP-forming)
Comments: The enzyme is part of a dimethylsulfoniopropanoate demethylation pathway in the marine bacteria Ruegeria pomeroyi and Pelagibacter ubique. It also occurs in some nonmarine bacteria capable of metabolizing dimethylsulfoniopropionate (e.g. Burkholderia thailandensis, Pseudomonas aeruginosa, and Silicibacter lacuscaerulensis). It requires Mg2+ [2].
References:
1.  Reisch, C.R., Stoudemayer, M.J., Varaljay, V.A., Amster, I.J., Moran, M.A. and Whitman, W.B. Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria. Nature 473 (2011) 208–211. [PMID: 21562561]
2.  Bullock, H.A., Reisch, C.R., Burns, A.S., Moran, M.A. and Whitman, W.B. Regulatory and functional diversity of methylmercaptopropionate coenzyme A ligases from the dimethylsulfoniopropionate demethylation pathway in Ruegeria pomeroyi DSS-3 and other proteobacteria. J. Bacteriol. 196 (2014) 1275–1285. [PMID: 24443527]
[EC 6.2.1.44 created 2014]
 
 
EC 6.2.1.45     
Accepted name: E1 ubiquitin-activating enzyme
Reaction: ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Other name(s): ubiquitin activating enzyme; E1; ubiquitin-activating enzyme E1
Systematic name: ubiquitin:[E1 ubiquitin-activating enzyme] ligase (AMP-forming)
Comments: Catalyses the ATP-dependent activation of ubiquitin through the formation of a thioester bond between the C-terminal glycine of ubiquitin and the sulfhydryl side group of a cysteine residue in the E1 protein. The two-step reaction consists of the ATP-dependent formation of an E1-ubiquitin adenylate intermediate in which the C-terminal glycine of ubiquitin is bound to AMP via an acyl-phosphate linkage, then followed by the conversion to an E1-ubiquitin thioester bond via the cysteine residue on E1 in the second step.
References:
1.  Haas, A.L., Warms, J.V., Hershko, A. and Rose, I.A. Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation. J. Biol. Chem. 257 (1982) 2543–2548. [PMID: 6277905]
2.  Huzil, J.T., Pannu, R., Ptak, C., Garen, G. and Ellison, M.J. Direct catalysis of lysine 48-linked polyubiquitin chains by the ubiquitin-activating enzyme. J. Biol. Chem. 282 (2007) 37454–37460. [PMID: 17951259]
3.  Zheng, M., Liu, J., Yang, Z., Gu, X., Li, F., Lou, T., Ji, C. and Mao, Y. Expression, purification and characterization of human ubiquitin-activating enzyme, UBE1. Mol. Biol. Rep. 37 (2010) 1413–1419. [PMID: 19343538]
4.  Carvalho, A.F., Pinto, M.P., Grou, C.P., Vitorino, R., Domingues, P., Yamao, F., Sa-Miranda, C. and Azevedo, J.E. High-yield expression in Escherichia coli and purification of mouse ubiquitin-activating enzyme E1. Mol Biotechnol 51 (2012) 254–261. [PMID: 22012022]
[EC 6.2.1.45 created 2015]
 
 
EC 6.2.1.46     
Accepted name: L-allo-isoleucine—holo-[CmaA peptidyl-carrier protein] ligase
Reaction: ATP + L-allo-isoleucine + holo-[CmaA peptidyl-carrier protein] = AMP + diphosphate + L-allo-isoleucyl-[CmaA peptidyl-carrier protein]
Other name(s): CmaA
Systematic name: L-allo-isoleucine:holo-[CmaA peptidyl-carrier protein] ligase (AMP-forming)
Comments: This two-domain protein from the bacterium Pseudomonas syringae contains an adenylation domain (A domain) and a thiolation domain (T domain). It catalyses the adenylation of L-allo-isoleucine and its attachment to the T domain. The enzyme is involved in the biosynthesis of the toxin coronatine, which mimics the plant hormone jasmonic acid isoleucine. Coronatine promotes opening of the plant stomata allowing bacterial invasion, which is followed by bacterial growth in the apoplast, systemic susceptibility, and disease.
References:
1.  Couch, R., O'Connor, S.E., Seidle, H., Walsh, C.T. and Parry, R. Characterization of CmaA, an adenylation-thiolation didomain enzyme involved in the biosynthesis of coronatine. J. Bacteriol. 186 (2004) 35–42. [PMID: 14679222]
[EC 6.2.1.46 created 2015]
 
 
EC 6.2.1.47     
Accepted name: medium-chain-fatty-acid—[acyl-carrier-protein] ligase
Reaction: ATP + a medium-chain fatty acid + a holo-[acyl-carrier protein] = AMP + diphosphate + a medium-chain acyl-[acyl-carrier protein]
Other name(s): jamA (gene name)
Systematic name: medium-chain-fatty-acid:[acyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme ligates medium chain fatty acids (with aliphatic chain of 6-12 carbons) to an acyl-carrier protein.
References:
1.  Edwards, D.J., Marquez, B.L., Nogle, L.M., McPhail, K., Goeger, D.E., Roberts, M.A. and Gerwick, W.H. Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem. Biol. 11 (2004) 817–833. [PMID: 15217615]
2.  Zhu, X., Liu, J. and Zhang, W. De novo biosynthesis of terminal alkyne-labeled natural products. Nat. Chem. Biol. 11 (2015) 115–120. [PMID: 25531891]
[EC 6.2.1.47 created 2016]
 
 
EC 6.2.1.48     
Accepted name: carnitine—CoA ligase
Reaction: ATP + L-carnitine + CoA = AMP + diphosphate + L-carnitinyl-CoA
Glossary: carnitine = 3-hydroxy-4-(trimethylammonio)butanoate
crotonobetaine = (E)-4-(trimethylammonio)but-2-enoate
γ-butyrobetaine = 4-(trimethylammonio)butanoate
Other name(s): caiC (gene name)
Systematic name: L-carnitine:CoA ligase (AMP-forming)
Comments: The enzyme, originally characterized from the bacterium Escherichia coli, can catalyse the transfer of CoA to L-carnitine, crotonobetaine and γ-butyrobetaine. In vitro the enzyme also exhibits the activity of EC 2.8.3.21, L-carnitine CoA-transferase.
References:
1.  Eichler, K., Bourgis, F., Buchet, A., Kleber, H.P. and Mandrand-Berthelot, M.A. Molecular characterization of the cai operon necessary for carnitine metabolism in Escherichia coli. Mol. Microbiol. 13 (1994) 775–786. [PMID: 7815937]
2.  Bernal, V., Arense, P., Blatz, V., Mandrand-Berthelot, M.A., Canovas, M. and Iborra, J.L. Role of betaine:CoA ligase (CaiC) in the activation of betaines and the transfer of coenzyme A in Escherichia coli. J. Appl. Microbiol. 105 (2008) 42–50. [PMID: 18266698]
[EC 6.2.1.48 created 2017]
 
 
EC 6.2.1.49     
Accepted name: long-chain fatty acid adenylyltransferase FadD28
Reaction: ATP + a long-chain fatty acid + holo-[mycocerosate synthase] = AMP + diphosphate + a long-chain acyl-[mycocerosate synthase] (overall reaction)
(1a) ATP + a long-chain fatty acid = diphosphate + a long-chain acyl-adenylate ester
(1b) a long-chain acyl-adenylate ester + holo-[mycocerosate synthase] = AMP + a long-chain acyl-[mycocerosate synthase]
Other name(s): fadD28 (gene name)
Systematic name: long-chain fatty acid:holo-[mycocerosate synthase] ligase (AMP-forming)
Comments: The enzyme, found in certain mycobacteria, activates long-chain fatty acids by adenylation and transfers them to EC 2.3.1.111, mycocerosate synthase. The enzyme participates in the biosynthesis of the virulent lipids dimycocerosates (DIM) and dimycocerosyl triglycosyl phenolphthiocerol (PGL).
References:
1.  Fitzmaurice, A.M. and Kolattukudy, P.E. Open reading frame 3, which is adjacent to the mycocerosic acid synthase gene, is expressed as an acyl coenzyme A synthase in Mycobacterium bovis BCG. J. Bacteriol. 179 (1997) 2608–2615. [PMID: 9098059]
2.  Goyal, A., Yousuf, M., Rajakumara, E., Arora, P., Gokhale, R.S. and Sankaranarayanan, R. Crystallization and preliminary X-ray crystallographic studies of the N-terminal domain of FadD28, a fatty-acyl AMP ligase from Mycobacterium tuberculosis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 (2006) 350–352. [PMID: 16582482]
3.  Arora, P., Goyal, A., Natarajan, V.T., Rajakumara, E., Verma, P., Gupta, R., Yousuf, M., Trivedi, O.A., Mohanty, D., Tyagi, A., Sankaranarayanan, R. and Gokhale, R.S. Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis. Nat. Chem. Biol. 5 (2009) 166–173. [PMID: 19182784]
4.  Menendez-Bravo, S., Comba, S., Sabatini, M., Arabolaza, A. and Gramajo, H. Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli. Metab. Eng. 24 (2014) 97–106. [PMID: 24831705]
5.  Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040–1050. [PMID: 25561717]
[EC 6.2.1.49 created 2016 as EC 2.7.7.95, transferred 2017 to EC 6.2.1.49]
 
 
EC 6.2.1.50     
Accepted name: 4-hydroxybenzoate adenylyltransferase FadD22
Reaction: ATP + 4-hydroxybenzoate + holo-[4-hydroxyphenylalkanoate synthase] = AMP + diphosphate + 4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase] (overall reaction)
(1a) ATP + 4-hydroxybenzoate = 4-hydroxybenzoyl-adenylate + diphosphate
(1b) 4-hydroxybenzoyl-adenylate + holo-[4-hydroxyphenylalkanoate synthase] = AMP + 4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase]
Other name(s): fadD22 (gene name); 4-hydroxybenzoate adenylase
Systematic name: 4-hydroxybenzoate:holo-[4-hydroxyphenylalkanoate synthase] ligase (AMP-forming)
Comments: This mycobacterial enzyme participates in the biosynthesis of phenolphthiocerols. Following the substrate’s activation by adenylation, it is transferred to an acyl-carrier protein domain within the enzyme, from which it is transferred to EC 2.3.1.261, 4-hydroxyphenylalkanoate synthase.
References:
1.  Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715–2725. [PMID: 20553505]
2.  Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040–1050. [PMID: 25561717]
[EC 6.2.1.50 created 2017 as EC 2.7.7.98, transferred 2017 to EC 6.2.1.50]
 
 
EC 6.2.1.51     
Accepted name: 4-hydroxyphenylalkanoate adenylyltransferase FadD29
Reaction: (1) ATP + 17-(4-hydroxyphenyl)heptadecanoate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + 17-(4-hydroxyphenyl)heptadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(1a) ATP + 17-(4-hydroxyphenyl)heptadecanoate = diphosphate + 17-(4-hydroxyphenyl)heptadecanoyl-adenylate
(1b) 17-(4-hydroxyphenyl)heptadecanoyl-adenylate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + 17-(4-hydroxyphenyl)heptadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(2) ATP + 19-(4-hydroxyphenyl)nonadecanoate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + 19-(4-hydroxyphenyl)nonadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(2a) ATP + 19-(4-hydroxyphenyl)nonadecanoate = diphosphate + 19-(4-hydroxyphenyl)nonadecanoyl-adenylate
(2b) 19-(4-hydroxyphenyl)nonadecanoyl-adenylate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + 19-(4-hydroxyphenyl)nonadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
Other name(s): fadD29 (gene name); 4-hydroxyphenylalkanoate adenylase
Systematic name: 4-hydroxyphenylalkanoate:holo-[(phenol)carboxyphthiodiolenone synthase] ligase
Comments: The mycobacterial enzyme participates in the biosynthesis of phenolphthiocerols. Following the substrate’s activation by adenylation, it is transferred to an acyl-carrier protein domain within the enzyme, from which it is transferred to the phenolphthiocerol/phthiocerol polyketide synthase.
References:
1.  Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715–2725. [PMID: 20553505]
2.  Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040–1050. [PMID: 25561717]
[EC 6.2.1.51 created 2016 as EC 2.7.7.94, transferred 2017 to EC 6.2.1.51]
 
 
EC 6.2.1.52     
Accepted name: L-firefly luciferin—CoA ligase
Reaction: ATP + L-firefly luciferin + CoA = AMP + diphosphate + L-firefly luciferyl-CoA
Glossary: L-firefly luciferin = (R)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate
Other name(s): LUC
Systematic name: (R)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate:CoA ligase (AMP-forming)
Comments: This is an alternative activity of the firefly luciferase (EC 1.13.12.7), which the enzyme exhibits under normal conditions only when acting on the L-enantiomer of its substrate. The D-isomer can act as a substrate for the CoA—ligase activity in vitro only under low oxygen conditions that are not found in vivo. The activation of L-firefly luciferin to a CoA ester is a step in a recycling pathway that results in its epimerization to the D enantiomer, which is the only substrate whose oxygenation results in light emission.
References:
1.  Fraga, H., Esteves da Silva, J.C. and Fontes, R. Identification of luciferyl adenylate and luciferyl coenzyme a synthesized by firefly luciferase. Chembiochem 5 (2004) 110–115. [PMID: 14695520]
2.  Nakamura, M., Maki, S., Amano, Y., Ohkita, Y., Niwa, K., Hirano, T., Ohmiya, Y. and Niwa, H. Firefly luciferase exhibits bimodal action depending on the luciferin chirality. Biochem. Biophys. Res. Commun. 331 (2005) 471–475. [PMID: 15850783]
3.  Viviani, V.R., Scorsato, V., Prado, R.A., Pereira, J.G., Niwa, K., Ohmiya, Y. and Barbosa, J.A. The origin of luciferase activity in Zophobas mealworm AMP/CoA-ligase (protoluciferase): luciferin stereoselectivity as a switch for the oxygenase activity. Photochem Photobiol Sci 9 (2010) 1111–1119. [PMID: 20526507]
4.  Maeda, J., Kato, D.I., Okuda, M., Takeo, M., Negoro, S., Arima, K., Ito, Y. and Niwa, K. Biosynthesis-inspired deracemizative production of D-luciferin by combining luciferase and thioesterase. Biochim. Biophys. Acta 1861 (2017) 2112–2118. [PMID: 28454735]
[EC 6.2.1.52 created 2017]
 
 
EC 6.2.1.53     
Accepted name: L-proline—[L-prolyl-carrier protein] ligase
Reaction: ATP + L-proline + holo-[L-prolyl-carrier protein] = AMP + diphosphoate + L-prolyl-[L-prolyl-carrier protein] (overall reaction)
(1a) ATP + L-proline = diphosphate + (L-prolyl)adenylate
(1b) (L-prolyl)adenylate + holo-[L-prolyl-carrier protein] = AMP + L-prolyl-[L-prolyl-carrier protein]
Other name(s): pltF (gene name); bmp4 (gene name); pigI (gene name)
Systematic name: L-proline:[L-prolyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme participates in the biosynthesis of several pyrrole-containing compounds, such as undecylprodigiosin, prodigiosin, pyoluteorin, and coumermycin A1. It catalyses the activation of L-proline to an adenylate form, followed by its transfer to the 4′-phosphopantheine moiety of an L-prolyl-carrier protein.
References:
1.  Thomas, M.G., Burkart, M.D. and Walsh, C.T. Conversion of L-proline to pyrrolyl-2-carboxyl-S-PCP during undecylprodigiosin and pyoluteorin biosynthesis. Chem. Biol. 9 (2002) 171–184. [PMID: 11880032]
2.  Harris, A.K., Williamson, N.R., Slater, H., Cox, A., Abbasi, S., Foulds, I., Simonsen, H.T., Leeper, F.J. and Salmond, G.P. The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology 150 (2004) 3547–3560. [PMID: 15528645]
3.  Williamson, N.R., Simonsen, H.T., Ahmed, R.A., Goldet, G., Slater, H., Woodley, L., Leeper, F.J. and Salmond, G.P. Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces. Mol. Microbiol. 56 (2005) 971–989. [PMID: 15853884]
[EC 6.2.1.53 created 2018]
 
 
EC 6.2.1.54     
Accepted name: D-alanine—[D-alanyl-carrier protein] ligase
Reaction: ATP + D-alanine + holo-[D-alaninyl-carrier protein] = AMP + diphosphate + D-alanyl-[D-alanyl-carrier protein] (overall reaction)
(1a) ATP + D-alanine = (D-alanyl)adenylate + diphosphate
(1b) (D-alanyl)adenylate + holo-[D-alanyl-carrier protein] = AMP + D-alanyl-[D-alanyl-carrier protein]
Other name(s): dltA (gene name); Dcl
Systematic name: D-alanine:[D-alanyl-carrier protein] ligase
Comments: The enzyme is involved in the modification of wall teichoic acids, as well as type I and IV lipoteichoic acids, with D-alanine residues. It activates D-alanine using ATP to form a high-energy (D-alanyl)adenylate intermediate and subsequently transfers the alanyl moiety to the phosphopantheinyl prosthetic group of a D-alanyl-carrier protein (DltC).
References:
1.  Perego, M., Glaser, P., Minutello, A., Strauch, M.A., Leopold, K. and Fischer, W. Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. J. Biol. Chem. 270 (1995) 15598–15606. [PMID: 7797557]
2.  Yonus, H., Neumann, P., Zimmermann, S., May, J.J., Marahiel, M.A. and Stubbs, M.T. Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains. J. Biol. Chem. 283 (2008) 32484–32491. [PMID: 18784082]
3.  Du, L., He, Y. and Luo, Y. Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus. Biochemistry 47 (2008) 11473–11480. [PMID: 18847223]
4.  Osman, K.T., Du, L., He, Y. and Luo, Y. Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP. J. Mol. Biol. 388 (2009) 345–355. [PMID: 19324056]
[EC 6.2.1.54 created 2018]
 
 
EC 6.2.1.55     
Accepted name: E1 SAMP-activating enzyme
Reaction: ATP + [SAMP]-Gly-Gly + [E1 SAMP-activating enzyme]-L-cysteine = S-[[SAMP]-Gly-Gly]-[[E1 SAMP-activating enzyme]-L-cysteine] + AMP + diphosphate (overall reaction)
(1a) ATP + [SAMP]-Gly-Gly = diphosphate + [SAMP]-Gly-Gly-AMP
(1b) [SAMP]-Gly-Gly-AMP + [E1 SAMP-activating enzyme]-L-cysteine = S-[[SAMP]-Gly-Gly]-[[E1 SAMP-activating enzyme]-L-cysteine] + AMP
Glossary: SAMP = small archaeal modifier protein = ubiquitin-like small archaeal modifier protein
Other name(s): UbaA; SAMP-activating enzyme E1
Systematic name: [SAMP]:[E1 SAMP-activating enzyme] ligase (AMP-forming)
Comments: Contains Zn2+. The enzyme catalyses the activation of SAMPs (Small Archaeal Modifier Proteins), which are ubiquitin-like proteins found only in the Archaea. SAMPs are involved in protein degradation, and also act as sulfur carriers involved in thiolation of tRNA and other metabolites such as molybdopterin. The enzyme catalyses the ATP-dependent formation of a SAMP adenylate intermediate in which the C-terminal glycine of SAMP is bound to AMP via an acyl-phosphate linkage (reaction 1). This intermediate can accept a sulfur atom to form a thiocarboxylate moiety in a mechanism that is not yet understood. Alternatively, the E1 enzyme can transfer SAMP from its activated form to an internal cysteine residue, releasing AMP (reaction 2). In this case SAMP is subsequently transferred to a lysine residue in a target protein in a process termed SAMPylation. Auto-SAMPylation (attachment of SAMP to lysine residues within the E1 enzyme) has been observed. cf. EC 2.7.7.100, SAMP-activating enzyme.
References:
1.  Miranda, H.V., Nembhard, N., Su, D., Hepowit, N., Krause, D.J., Pritz, J.R., Phillips, C., Soll, D. and Maupin-Furlow, J.A. E1- and ubiquitin-like proteins provide a direct link between protein conjugation and sulfur transfer in archaea. Proc. Natl Acad. Sci. USA 108 (2011) 4417–4422. [PMID: 21368171]
2.  Maupin-Furlow, J.A. Ubiquitin-like proteins and their roles in archaea. Trends Microbiol 21 (2013) 31–38. [PMID: 23140889]
3.  Miranda, H.V., Antelmann, H., Hepowit, N., Chavarria, N.E., Krause, D.J., Pritz, J.R., Basell, K., Becher, D., Humbard, M.A., Brocchieri, L. and Maupin-Furlow, J.A. Archaeal ubiquitin-like SAMP3 is isopeptide-linked to proteins via a UbaA-dependent mechanism. Mol. Cell. Proteomics 13 (2014) 220–239. [PMID: 24097257]
4.  Hepowit, N.L., de Vera, I.M., Cao, S., Fu, X., Wu, Y., Uthandi, S., Chavarria, N.E., Englert, M., Su, D., Söll, D., Kojetin, D.J. and Maupin-Furlow, J.A. Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea. FEBS J. 283 (2016) 3567–3586. [PMID: 27459543]
[EC 6.2.1.55 created 2018]
 
 
EC 6.3.1.1     
Accepted name: aspartate—ammonia ligase
Reaction: ATP + L-aspartate + NH3 = AMP + diphosphate + L-asparagine
Other name(s): asparagine synthetase; L-asparagine synthetase
Systematic name: L-aspartate:ammonia ligase (AMP-forming)
References:
1.  Ravel, J.M., Norton, S.J., Humphreys, J.S. and Shive, W. Asparagine biosynthesis in Lactobacillus arabinosus and its control by asparagine through enzyme inhibition and repression. J. Biol. Chem. 237 (1962) 2845–2849. [PMID: 14490631]
2.  Webster, G.C. and Varner, J.E. Aspartate metabolism and asparagine synthesis in plant systems. J. Biol. Chem. 215 (1955) 91–99. [PMID: 14392145]
[EC 6.3.1.1 created 1961]
 
 
EC 6.3.1.2     
Accepted name: glutamine synthetase
Reaction: ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine
Other name(s): glutamate—ammonia ligase; glutamylhydroxamic synthetase; L-glutamine synthetase; GS
Systematic name: L-glutamate:ammonia ligase (ADP-forming)
Comments: Glutamine synthetase, which catalyses the incorporation of ammonium into glutamate, is a key enzyme of nitrogen metabolism found in all domains of life. Several types have been described, differing in their oligomeric structures and cofactor requirements.
References:
1.  Elliott, W.H. Isolation of glutamine synthetase and glutamotransferase from green peas. J. Biol. Chem. 201 (1953) 661–672. [PMID: 13061404]
2.  Fry, B.A. Glutamine synthesis by Micrococcus pyogenes var. aureus. Biochem. J. 59 (1955) 579–589. [PMID: 14363150]
3.  Lajtha, A., Mela, P. and Waelsch, H. Manganese-dependent glutamotransferase. J. Biol. Chem. 205 (1953) 553–564. [PMID: 13129232]
4.  Meister, A. Glutamine synthesis. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 6, Academic Press, New York, 1962, pp. 443–468.
5.  Woolfolk, C.A., Shapiro, B. and Stadtman, E.R. Regulation of glutamine synthetase. I. Purification and properties of glutamine synthetase from Escherichia coli. Arch. Biochem. Biophys. 116 (1966) 177–192. [PMID: 5336023]
6.  Kumada, Y., Benson, D.R., Hillemann, D., Hosted, T.J., Rochefort, D.A., Thompson, C.J., Wohlleben, W. and Tateno, Y. Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes. Proc. Natl. Acad. Sci. USA 90 (1993) 3009–3013. [PMID: 8096645]
7.  Llorca, O., Betti, M., Gonzalez, J.M., Valencia, A., Marquez, A.J. and Valpuesta, J.M. The three-dimensional structure of an eukaryotic glutamine synthetase: functional implications of its oligomeric structure. J. Struct. Biol. 156 (2006) 469–479. [PMID: 16884924]
8.  Martinez-Espinosa, R.M., Esclapez, J., Bautista, V. and Bonete, M.J. An octameric prokaryotic glutamine synthetase from the haloarchaeon Haloferax mediterranei. FEMS Microbiol. Lett. 264 (2006) 110–116. [PMID: 17020556]
[EC 6.3.1.2 created 1961, modified 2016]
 
 
EC 6.3.1.3      
Transferred entry: phosphoribosyl-glycinamide synthetase. Now EC 6.3.4.13, phosphoribosylamine—glycine ligase
[EC 6.3.1.3 created 1961, deleted 1972]
 
 
EC 6.3.1.4     
Accepted name: aspartate—ammonia ligase (ADP-forming)
Reaction: ATP + L-aspartate + NH3 = ADP + phosphate + L-asparagine
Other name(s): asparagine synthetase (ADP-forming); asparagine synthetase (adenosine diphosphate-forming)
Systematic name: L-aspartate:ammonia ligase (ADP-forming)
References:
1.  Nair, P.M. Asparagine synthetase from γ-irradiated potatoes. Arch. Biochem. Biophys. 133 (1969) 208–215. [PMID: 5820987]
[EC 6.3.1.4 created 1972]
 
 
EC 6.3.1.5     
Accepted name: NAD+ synthase
Reaction: ATP + deamido-NAD+ + NH3 = AMP + diphosphate + NAD+
Other name(s): NAD synthetase; NAD synthase; nicotinamide adenine dinucleotide synthetase; diphosphopyridine nucleotide synthetase
Systematic name: deamido-NAD+:ammonia ligase (AMP-forming)
Comments: L-Glutamine also acts, more slowly, as amido-donor [cf. EC 6.3.5.1].
References:
1.  Spencer, R.L. and Preiss, J. Biosynthesis of diphosphopyridine nucleotide. The purification and the properties of diphosphopyridine nucleotide synthetase from Escherichia coli B. J. Biol. Chem. 242 (1967) 385–392. [PMID: 4290215]
[EC 6.3.1.5 created 1972]
 
 
EC 6.3.1.6     
Accepted name: glutamate—ethylamine ligase
Reaction: ATP + L-glutamate + ethylamine = ADP + phosphate + N5-ethyl-L-glutamine
Other name(s): N5-ethyl-L-glutamine synthetase; theanine synthetase; N5-ethylglutamine synthetase
Systematic name: L-glutamate:ethylamine ligase (ADP-forming)
References:
1.  Sasaoka, K. and Kito, M. Synthesis of theanine by tea seedling homogenate. Agric. Biol. Chem. 28 (1964) 313–317.
2.  Sasaoka, K., Kito, M. and Inagaki, H. Studies on the biosynthesis of theanine in tea seedlings. Synthesis of theanine by the homogenate of tea seedlings. Agric. Biol. Chem. 27 (1963) 467–468.
3.  Sasaoka, K., Kito, M. and Onishi, Y. Some properties of the theanine synthesizing enzyme in tea seedlings. Agric. Biol. Chem. 29 (1965) 984–988.
[EC 6.3.1.6 created 1976]
 
 
EC 6.3.1.7     
Accepted name: 4-methyleneglutamate—ammonia ligase
Reaction: ATP + 4-methylene-L-glutamate + NH3 = AMP + diphosphate + 4-methylene-L-glutamine
Other name(s): 4-methyleneglutamine synthetase
Systematic name: 4-methylene-L-glutamate:ammonia ligase (AMP-forming)
Comments: Glutamine can act instead of NH3, but more slowly.
References:
1.  Winter, H.C., Su, T.-Z. and Dekker, E.E. 4-Methyleneglutamine synthetase: a new amide synthetase present in germinating peanuts. Biochem. Biophys. Res. Commun. 111 (1983) 484–489. [PMID: 6838571]
[EC 6.3.1.7 created 1986]
 
 
EC 6.3.1.8     
Accepted name: glutathionylspermidine synthase
Reaction: glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate
Glossary: glutathione = γ-L-glutamyl-L-cysteinyl-glycine
spermidine = N-(3-aminopropyl)butane-1,4-diamine
Other name(s): glutathione:spermidine ligase (ADP-forming)
Systematic name: γ-L-glutamyl-L-cysteinyl-glycine:spermidine ligase (ADP-forming) [spermidine is numbered so that atom N-1 is in the amino group of the aminopropyl part of the molecule]
Comments: Requires magnesium ions. Involved in the synthesis of trypanothione in trypanosomatids. The enzyme from Escherichia coli is bifunctional and also catalyses the glutathionylspermidine amidase (EC 3.5.1.78) reaction, resulting in a net hydrolysis of ATP.
References:
1.  Smith, K., Nadeau, K., Bradley, M., Walsh, C.T., Fairlamb, A.H. Purification of glutathionylspermidine and trypanothione synthase from Crithidia fasciculata. Protein Sci. 1 (1992) 874–883. [PMID: 1304372]
2.  Bollinger, J.M., Kwon, D.S., Huisman, G.W., Kolter, R., Walsh, C.T. Glutathionylspermidine metabolism in E. coli. Purification, cloning, overproduction and characterization of a bifunctional glutathionylspermidine synthetase/amidase. J. Biol. Chem. 270 (1995) 14031–14041. [PMID: 7775463]
[EC 6.3.1.8 created 1999]
 
 
EC 6.3.1.9     
Accepted name: trypanothione synthase
Reaction: (1) glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate
(2) glutathione + glutathionylspermidine + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
Glossary: N1,N8-bis(glutathionyl)spermidine = trypanothione
Other name(s): glutathionylspermidine:glutathione ligase (ADP-forming)
Systematic name: spermidine/glutathionylspermidine:glutathione ligase (ADP-forming)
Comments: The enzyme, characterized from several trypanosomatids (e.g. Trypanosoma cruzi) catalyses two subsequent reactions, leading to production of trypanothione from glutathione and spermidine. Some trypanosomatids (e.g. Crithidia species and some Leishmania species) also contain an enzyme that only carries out the first reaction (cf. EC 6.3.1.8, glutathionylspermidine synthase). The enzyme is bifunctional, and also catalyses the hydrolysis of glutathionylspermidine and trypanothione (cf. EC 3.5.1.78, glutathionylspermidine amidase).
References:
1.  Smith, K., Nadeau, K., Bradley, M., Walsh, C.T., Fairlamb, A.H. Purification of glutathionylspermidine and trypanothione synthase from Crithidia fasciculata. Protein Sci. 1 (1992) 874–883. [PMID: 1304372]
2.  Oza, S.L., Tetaud, E., Ariyanayagam, M.R., Warnon, S.S. and Fairlamb, A.H. A single enzyme catalyses formation of trypanothione from glutathione and spermidine in Trypanosoma cruzi. J. Biol. Chem. 277 (2002) 35853–35861. [PMID: 12121990]
3.  Comini, M., Menge, U., Wissing, J. and Flohe, L. Trypanothione synthesis in crithidia revisited. J. Biol. Chem. 280 (2005) 6850–6860. [PMID: 15537651]
4.  Oza, S.L., Shaw, M.P., Wyllie, S. and Fairlamb, A.H. Trypanothione biosynthesis in Leishmania major. Mol. Biochem. Parasitol. 139 (2005) 107–116. [PMID: 15610825]
5.  Fyfe, P.K., Oza, S.L., Fairlamb, A.H. and Hunter, W.N. Leishmania trypanothione synthetase-amidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities. J. Biol. Chem. 283 (2008) 17672–17680. [PMID: 18420578]
[EC 6.3.1.9 created 1999, modified 2014]
 
 
EC 6.3.1.10     
Accepted name: adenosylcobinamide-phosphate synthase
Reaction: (1) ATP + adenosylcobyric acid + (R)-1-aminopropan-2-yl phosphate = ADP + phosphate + adenosylcobinamide phosphate
(2) ATP + adenosylcobyric acid + (R)-1-aminopropan-2-ol = ADP + phosphate + adenosylcobinamide
Other name(s): CbiB
Systematic name: adenosylcobyric acid:(R)-1-aminopropan-2-yl phosphate ligase (ADP-forming)
Comments: One of the substrates for this reaction, (R)-1-aminopropan-2-yl phosphate, is produced by CobD (EC 4.1.1.81, threonine-phosphate decarboxylase).
References:
1.  Cheong, C.G., Bauer, C.B., Brushaber, K.R., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica. Biochemistry 41 (2002) 4798–4808. [PMID: 11939774]
2.  Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390–412. [PMID: 12195810]
[EC 6.3.1.10 created 2004]
 
 
EC 6.3.1.11     
Accepted name: glutamate—putrescine ligase
Reaction: ATP + L-glutamate + putrescine = ADP + phosphate + γ-L-glutamylputrescine
Glossary: putrescine = butane-1,4-diamine
Other name(s): γ-glutamylputrescine synthetase; YcjK
Systematic name: L-glutamate:putrescine ligase (ADP-forming)
Comments: Forms part of a novel bacterial putrescine utilization pathway in Escherichia coli.
References:
1.  Kurihara, S., Oda, S., Kato, K., Kim, H.G., Koyanagi, T., Kumagai, H. and Suzuki, H. A novel putrescine utilization pathway involves γ-glutamylated intermediates of Escherichia coli K-12. J. Biol. Chem. 280 (2005) 4602–4608. [PMID: 15590624]
[EC 6.3.1.11 created 2005]
 
 
EC 6.3.1.12     
Accepted name: D-aspartate ligase
Reaction: ATP + D-aspartate + [β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n = [β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-6-N-(β-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate
Other name(s): Aslfm; UDP-MurNAc-pentapeptide:D-aspartate ligase; D-aspartic acid-activating enzyme
Systematic name: D-aspartate:[β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n ligase (ADP-forming)
Comments: This enzyme forms part of the peptidoglycan assembly pathway of Gram-positive bacteria grown in medium containing D-Asp. Normally, the side chains the acylate the 6-amino group of the L-lysine residue contain L-Ala-L-Ala but these amino acids are replaced by D-Asp when D-Asp is included in the medium. Hybrid chains containing L-Ala-D-Asp, L-Ala-L-Ala-D-Asp or D-Asp-L-Ala are not formed [4]. The enzyme belongs in the ATP-grasp protein superfamily [3,4]. The enzyme is highly specific for D-aspartate, as L-aspartate, D-glutamate, D-alanine, D-iso-asparagine and D-malic acid are not substrates [4]. In Enterococcus faecium, the substrate D-aspartate is produced by EC 5.1.1.13, aspartate racemase [4]
References:
1.  Staudenbauer, W. and Strominger, J.L. Activation of D-aspartic acid for incorporation into peptidoglycan. J. Biol. Chem. 247 (1972) 5095–5102. [PMID: 4262567]
2.  Staudenbauer, W., Willoughby, E. and Strominger, J.L. Further studies of the D-aspartic acid-activating enzyme of Streptococcus faecalis and its attachment to the membrane. J. Biol. Chem. 247 (1972) 5289–5296. [PMID: 4626717]
3.  Galperin, M.Y. and Koonin, E.V. A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Protein Sci. 6 (1997) 2639–2643. [PMID: 9416615]
4.  Bellais, S., Arthur, M., Dubost, L., Hugonnet, J.E., Gutmann, L., van Heijenoort, J., Legrand, R., Brouard, J.P., Rice, L. and Mainardi, J.L. Aslfm, the D-aspartate ligase responsible for the addition of D-aspartic acid onto the peptidoglycan precursor of Enterococcus faecium. J. Biol. Chem. 281 (2006) 11586–11594. [PMID: 16510449]
[EC 6.3.1.12 created 2006]
 
 
EC 6.3.1.13     
Accepted name: L-cysteine:1D-myo-inositol 2-amino-2-deoxy-α-D-glucopyranoside ligase
Reaction: 1-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP = 1-O-[2-(L-cysteinamido)-2-deoxy-α-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate
Glossary: mycothiol = 1-O-[2-(N2-acetyl-L-cysteinamido)-2-deoxy--D-glucopyranosyl]-1D-myo-inositol
Other name(s): MshC; MshC ligase; Cys:GlcN-Ins ligase; mycothiol ligase
Systematic name: L-cysteine:1-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1D-myo-inositol ligase (AMP-forming)
Comments: This enzyme is a key enzyme in the biosynthesis of mycothiol, a small molecular weight thiol found in Mycobacteria spp. and other actinomycetes. Mycothiol plays a fundamental role in these organisms by helping to provide protection from the effects of reactive oxygen species and electrophiles, including many antibiotics. The enzyme may represent a novel target for new classes of antituberculars [2].
References:
1.  Fan, F., Luxenburger, A., Painter, G.F. and Blanchard, J.S. Steady-state and pre-steady-state kinetic analysis of Mycobacterium smegmatis cysteine ligase (MshC). Biochemistry 46 (2007) 11421–11429. [PMID: 17848100]
2.  Gutierrez-Lugo, M.T., Newton, G.L., Fahey, R.C. and Bewley, C.A. Cloning, expression and rapid purification of active recombinant mycothiol ligase as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S-transferase and maltose binding protein fusion proteins in Mycobacterium smegmatis. Protein Expr. Purif. 50 (2006) 128–136. [PMID: 16908186]
3.  Tremblay, L.W., Fan, F., Vetting, M.W. and Blanchard, J.S. The 1.6 Å crystal structure of Mycobacterium smegmatis MshC: the penultimate enzyme in the mycothiol biosynthetic pathway. Biochemistry 47 (2008) 13326–13335. [PMID: 19053270]
[EC 6.3.1.13 created 2009]
 
 
EC 6.3.1.14     
Accepted name: diphthine—ammonia ligase
Reaction: ATP + diphthine-[translation elongation factor 2] + NH3 = AMP + diphosphate + diphthamide-[translation elongation factor 2]
Glossary: translation elongation factor 2 = EF2 = eEF2
diphthine = 2-[(3S)-3-carboxy-3-(trimethylammonio)propyl]-L-histidine
diphthamide =2-[(3S)-3-carbamoyl-3-(trimethylammonio)propyl]-L-histidine
Other name(s): diphthamide synthase; diphthamide synthetase; DPH6 (gene name); ATPBD4 (gene name); diphthine:ammonia ligase (AMP-forming)
Systematic name: diphthine-[translation elongation factor 2]:ammonia ligase (AMP-forming)
Comments: This amidase catalyses the last step in the conversion of an L-histidine residue in the translation elongation factor EF2 to diphthamide. This factor is found in all archaebacteria and eukaryotes, but not in eubacteria, and is the target of bacterial toxins such as the diphtheria toxin and the Pseudomonas exotoxin A (see EC 2.4.2.36, NAD+—diphthamide ADP-ribosyltransferase). The substrate of the enzyme, diphthine, is produced by EC 2.1.1.98, diphthine synthase.
References:
1.  Moehring, T.J. and Moehring, J.M. Mutant cultured cells used to study the synthesis of diphthamide. UCLA Symp. Mol. Cell. Biol. New Ser. 45 (1987) 53–63.
2.  Moehring, J.M. and Moehring, T.J. The post-translational trimethylation of diphthamide studied in vitro. J. Biol. Chem. 263 (1988) 3840–3844. [PMID: 3346227]
3.  Su, X., Lin, Z., Chen, W., Jiang, H., Zhang, S. and Lin, H. Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. Proc. Natl. Acad. Sci. USA 109 (2012) 19983–19987. [PMID: 23169644]
[EC 6.3.1.14 created 1990 as EC 6.3.2.22, transferred 2010 to EC 6.3.1.14, modified 2013]
 
 
EC 6.3.1.15     
Accepted name: 8-demethylnovobiocic acid synthase
Reaction: ATP + 3-dimethylallyl-4-hydroxybenzoate + 3-amino-4,7-dihydroxycoumarin = AMP + diphosphate + 8-demethylnovobiocic acid
Glossary: 8-demethylnovobiocic acid = N-(2,7-dihydroxy-4-oxochromen-3-yl)-4-hydroxy-3-(3-methylbut-2-enyl)benzamide
Other name(s): novL (gene name); novobiocin ligase; novobiocic acid synthetase (misleading); 8-desmethyl-novobiocic acid synthetase; 8-demethylnovobiocic acid synthetase
Systematic name: 3-dimethylallyl-4-hydroxybenzoate:3-amino-4,7-dihydroxycoumarin ligase (AMP-forming)
Comments: The enzyme is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin.
References:
1.  Steffensky, M., Li, S.M. and Heide, L. Cloning, overexpression, and purification of novobiocic acid synthetase from Streptomyces spheroides NCIMB 11891. J. Biol. Chem. 275 (2000) 21754–21760. [PMID: 10801869]
2.  Pi, N., Meyers, C.L., Pacholec, M., Walsh, C.T. and Leary, J.A. Mass spectrometric characterization of a three-enzyme tandem reaction for assembly and modification of the novobiocin skeleton. Proc. Natl. Acad. Sci. USA 101 (2004) 10036–10041. [PMID: 15218104]
3.  Pacholec, M., Tao, J. and Walsh, C.T. CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry 44 (2005) 14969–14976. [PMID: 16274243]
[EC 6.3.1.15 created 2013]
 
 
EC 6.3.1.16      
Transferred entry: carbapenam-3-carboxylate synthetase. The enzyme was discovered at the public-review stage to have been misclassified and so was withdrawn. See EC 6.3.3.6, carbapenam-3-carboxylate synthase
[EC 6.3.1.16 created 2013, deleted 2013]
 
 
EC 6.3.1.17     
Accepted name: β-citrylglutamate synthase
Reaction: ATP + citrate + L-glutamate = ADP + phosphate + β-citryl-L-glutamate
Other name(s): NAAG synthetase I; NAAGS-I; RIMKLB (gene name) (ambiguous)
Systematic name: citrate:L-glutamate ligase (ADP-forming)
Comments: The enzyme, found in animals, also has the activity of EC 6.3.2.41, N-acetylaspartylglutamate synthase.
References:
1.  Collard, F., Stroobant, V., Lamosa, P., Kapanda, C.N., Lambert, D.M., Muccioli, G.G., Poupaert, J.H., Opperdoes, F. and Van Schaftingen, E. Molecular identification of N-acetylaspartylglutamate synthase and β-citrylglutamate synthase. J. Biol. Chem. 285 (2010) 29826–29833. [PMID: 20657015]
[EC 6.3.1.17 created 2014]
 
 
EC 6.3.1.18     
Accepted name: γ-glutamylanilide synthase
Reaction: ATP + L-glutamate + aniline = ADP + phosphate + N5-phenyl-L-glutamine
Glossary: γ-glutamylanilide = N5-phenyl-L-glutamine
Other name(s): atdA1 (gene name); tdnQ (gene name); dcaQ (gene name)
Systematic name: L-glutamate:aniline ligase (ADP-forming)
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Acinetobacter sp. YAA, catalyses the first step in the degradation of aniline. It can also accept chlorinated and methylated forms of aniline, preferrably in the o- and p-positions.
References:
1.  Takeo, M., Ohara, A., Sakae, S., Okamoto, Y., Kitamura, C., Kato, D. and Negoro, S. Function of a glutamine synthetase-like protein in bacterial aniline oxidation via γ-glutamylanilide. J. Bacteriol. 195 (2013) 4406–4414. [PMID: 23893114]
[EC 6.3.1.18 created 2014]
 
 
EC 6.3.1.19     
Accepted name: prokaryotic ubiquitin-like protein ligase
Reaction: ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine = ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-γ-L-glutamyl)-[protein]-L-lysine
Other name(s): PafA (ambiguous); Pup ligase; proteasome accessory factor A
Systematic name: [prokaryotic ubiquitin-like protein]:[protein]-L-lysine
Comments: The enzyme has been characterized from the bacteria Mycobacterium tuberculosis and Corynebacterium glutamicum. It catalyses the ligation of the prokaryotic ubiquitin-like protein (Pup) to a target protein by forming a bond between an ε-amino group of a lysine residue of the target protein and the γ-carboxylate of the C-terminal glutamate of the ubiquitin-like protein (Pup). The attachment of Pup, also known as Pupylation, marks proteins for proteasomal degradation.
References:
1.  Sutter, M., Damberger, F.F., Imkamp, F., Allain, F.H. and Weber-Ban, E. Prokaryotic ubiquitin-like protein (Pup) is coupled to substrates via the side chain of its C-terminal glutamate. J. Am. Chem. Soc. 132 (2010) 5610–5612. [PMID: 20355727]
2.  Guth, E., Thommen, M. and Weber-Ban, E. Mycobacterial ubiquitin-like protein ligase PafA follows a two-step reaction pathway with a phosphorylated pup intermediate. J. Biol. Chem. 286 (2011) 4412–4419. [PMID: 21081505]
3.  Ofer, N., Forer, N., Korman, M., Vishkautzan, M., Khalaila, I. and Gur, E. Allosteric transitions direct protein tagging by PafA, the prokaryotic ubiquitin-like protein (Pup) ligase. J. Biol. Chem. 288 (2013) 11287–11293. [PMID: 23471967]
4.  Barandun, J., Delley, C.L., Ban, N. and Weber-Ban, E. Crystal structure of the complex between prokaryotic ubiquitin-like protein and its ligase PafA. J. Am. Chem. Soc. 135 (2013) 6794–6797. [PMID: 23601177]
5.  Striebel, F., Imkamp, F., Özcelik, D. and Weber-Ban, E. Pupylation as a signal for proteasomal degradation in bacteria. Biochim. Biophys. Acta 1843 (2014) 103–113. [PMID: 23557784]
[EC 6.3.1.19 created 2015]
 
 
EC 6.3.1.20     
Accepted name: lipoate—protein ligase
Reaction: ATP + (R)-lipoate + a [lipoyl-carrier protein]-L-lysine = a [lipoyl-carrier protein]-N6-(lipoyl)lysine + AMP + diphosphate (overall reaction)
(1a) ATP + (R)-lipoate = lipoyl-AMP + diphosphate
(1b) lipoyl-AMP + a [lipoyl-carrier protein]-L-lysine = a [lipoyl-carrier protein]-N6-(lipoyl)lysine + AMP
Other name(s): lplA (gene name); lplJ (gene name); lipoate protein ligase; lipoate-protein ligase A; LPL; LPL-B
Systematic name: [lipoyl-carrier protein]-L-lysine:lipoate ligase (AMP-forming)
Comments: Requires Mg2+. This enzyme participates in lipoate salvage, and is responsible for lipoylation in the presence of exogenous lipoic acid [7]. The enzyme attaches lipoic acid to the lipoyl domains of certain key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [6]. Lipoylation is essential for the function of these enzymes. The enzyme can also use octanoate instead of lipoate.
References:
1.  Morris, T.W., Reed, K.E. and Cronan, J.E., Jr. Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. J. Biol. Chem. 269 (1994) 16091–16100. [PMID: 8206909]
2.  Green, D.E., Morris, T.W., Green, J., Cronan, J.E., Jr. and Guest, J.R. Purification and properties of the lipoate protein ligase of Escherichia coli. Biochem. J. 309 (1995) 853–862. [PMID: 7639702]
3.  Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [PMID: 14700636]
4.  Kim do, J., Kim, K.H., Lee, H.H., Lee, S.J., Ha, J.Y., Yoon, H.J. and Suh, S.W. Crystal structure of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with lipoyl domains. J. Biol. Chem. 280 (2005) 38081–38089. [PMID: 16141198]
5.  Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A. and Taniguchi, H. Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site. J. Biol. Chem. 280 (2005) 33645–33651. [PMID: 16043486]
6.  Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [PMID: 9218413]
7.  Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480]
[EC 6.3.1.20 created 2006 as EC 2.7.7.63, transferred 2016 to EC 6.3.1.20]
 
 
EC 6.3.2.1     
Accepted name: pantoate—β-alanine ligase (AMP-forming)
Reaction: ATP + (R)-pantoate + β-alanine = AMP + diphosphate + (R)-pantothenate
Glossary: (R)-pantoate = (2R)-2,4-dihydroxy-3,3-dimethylbutanoate
(R)-pantothenate = 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoate
Other name(s): pantothenate synthetase; pantoate activating enzyme; pantoic-activating enzyme; D-pantoate:β-alanine ligase (AMP-forming); pantoate—β-alanine ligase (ambiguous)
Systematic name: (R)-pantoate:β-alanine ligase (AMP-forming)
References:
1.  Ginoza, H.S. and Altenbern, R.A. The pantothenate-synthesizing enzyme cell-free extracts of Brucella abortus, strain 19. Arch. Biochem. Biophys. 56 (1955) 537–541. [PMID: 14377603]
2.  Maas, W.K. Pantothenate studies. III. Description of the extracted pantothenate-synthesizing enzyme of Escherichia coli. J. Biol. Chem. 198 (1952) 23–32. [PMID: 12999714]
3.  Maas, W.K. Mechanism of the enzymatic synthesis of pantothenate from β-alanine and pantoate. Fed. Proc. 15 (1956) 305–306.
[EC 6.3.2.1 created 1961, modified 2014]
 
 
EC 6.3.2.2     
Accepted name: glutamate—cysteine ligase
Reaction: ATP + L-glutamate + L-cysteine = ADP + phosphate + γ-L-glutamyl-L-cysteine
Other name(s): γ-glutamylcysteine synthetase; γ-glutamyl-L-cysteine synthetase; γ-glutamylcysteinyl synthetase
Systematic name: L-glutamate:L-cysteine γ-ligase (ADP-forming)
Comments: Can use L-aminohexanoate in place of glutamate.
References:
1.  MacKinnon, C.M., Carter, P.E., Smyth, S.J., Dunbar, B. and Fothergill, J.E. Molecular cloning of cDNA for human complement component C1s. The complete amino acid sequence. Eur. J. Biochem. 169 (1987) 547–553. [PMID: 3500856]
2.  Snoke, J.E., Yanari, S. and Bloch, K. Synthesis of glutathione from γ-glutamylcysteine. J. Biol. Chem. 201 (1953) 573–586. [PMID: 13061393]
3.  Mandeles, S. and Bloch, K. Enzymatic synthesis of γ-glutamylcysteine. J. Biol. Chem. 214 (1955) 639–646. [PMID: 14381401]
[EC 6.3.2.2 created 1961]
 
 
EC 6.3.2.3     
Accepted name: glutathione synthase
Reaction: ATP + γ-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione
Other name(s): glutathione synthetase; GSH synthetase
Systematic name: γ-L-glutamyl-L-cysteine:glycine ligase (ADP-forming)
References:
1.  Law, M.Y. and Halliwell, B. Purification and properties of glutathione synthetase from (Spinacia oleracea) leaves. Plant Sci. 43 (1986) 185–191.
2.  Macnicol, P.K. Homoglutathione and glutathione synthetases of legume seedlings - partial-purification and substrate-specificity. Plant Sci. 53 (1987) 229–235.
[EC 6.3.2.3 created 1961]
 
 
EC 6.3.2.4     
Accepted name: D-alanine—D-alanine ligase
Reaction: ATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanine
Other name(s): MurE synthetase [ambiguous]; alanine:alanine ligase (ADP-forming); alanylalanine synthetase
Systematic name: D-alanine:D-alanine ligase (ADP-forming)
Comments: Involved with EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate—L-alanine ligase), EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram).
References:
1.  Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. II. Enzymatic synthesis and addition of D-alanyl-D-alanine. J. Biol. Chem. 237 (1962) 2696–2703.
2.  Neuhaus, F.C. Kinetic studies on D-Ala-D-Ala synthetase. Fed. Proc. 21 (1962) 229.
3.  van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503–519. [PMID: 11699883]
[EC 6.3.2.4 created 1961, modified 2002]
 
 
EC 6.3.2.5     
Accepted name: phosphopantothenate—cysteine ligase (CTP)
Reaction: CTP + (R)-4′-phosphopantothenate + L-cysteine = CMP + diphosphate + N-[(R)-4′-phosphopantothenoyl]-L-cysteine
Other name(s): phosphopantothenoylcysteine synthetase (ambiguous); phosphopantothenate—cysteine ligase (ambiguous)
Systematic name: (R)-4′-phosphopantothenate:L-cysteine ligase
Comments: A key enzyme in the production of coenzyme A. The bacterial enzyme requires CTP, in contrast to the eukaryotic enzyme, EC 6.3.2.51, which requires ATP. Cysteine can be replaced by some of its derivatives.
References:
1.  Brown, G.M. The metabolism of pantothenic acid. J. Biol. Chem. 234 (1959) 370–378. [PMID: 13630913]
2.  Strauss, E., Kinsland, C., Ge, Y., McLafferty, F.W. and Begley, T.P. Phosphopantothenoylcysteine synthetase from Escherichia coli. Identification and characterization of the last unidentified Coenzyme A biosynthetic enzymes in bacteria. J. Biol. Chem. 276 (2001) 13513–13516. [PMID: 11278255]
3.  Kupke, T. Molecular characterization of the 4′-phosphopantothenoylcysteine synthetase domain of bacterial Dfp flavoproteins. J. Biol. Chem. 277 (2002) 36137–36145. [PMID: 12140293]
[EC 6.3.2.5 created 1961, modified 2003, modified 2017]
 
 
EC 6.3.2.6     
Accepted name: phosphoribosylaminoimidazolesuccinocarboxamide synthase
Reaction: ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
Other name(s): phosphoribosylaminoimidazole-succinocarboxamide synthetase; PurC; SAICAR synthetase; 4-(N-succinocarboxamide)-5-aminoimidazole synthetase; 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide synthetase; SAICARs; phosphoribosylaminoimidazolesuccinocarboxamide synthetase; 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase
Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate:L-aspartate ligase (ADP-forming)
Comments: Forms part of the purine biosynthesis pathway.
References:
1.  Lukens, L.N. and Buchanan, J.M. Biosynthesis of purines. XXIV. The enzymatic synthesis of 5-amino-1-ribosyl-4-imidazolecarboxylic acid 5′-phosphate from 5-amino-1-ribosylimidazole 5′-phosphate and carbon dioxide. J. Biol. Chem. 234 (1959) 1799–1805. [PMID: 13672967]
2.  Parker, J. Identification of the purC gene product of Escherichia coli. J. Bacteriol. 157 (1984) 712–717. [PMID: 6365889]
3.  Ebbole, D.J. and Zalkin, H. Cloning and characterization of a 12-gene cluster from Bacillus subtilis encoding nine enzymes for de novo purine nucleotide synthesis. J. Biol. Chem. 262 (1987) 8274–8287. [PMID: 3036807]
4.  Chen, Z.D., Dixon, J.E. and Zalkin, H. Cloning of a chicken liver cDNA encoding 5-aminoimidazole ribonucleotide carboxylase and 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase by functional complementation of Escherichia coli pur mutants. Proc. Natl. Acad. Sci. USA 87 (1990) 3097–3101. [PMID: 1691501]
5.  O'Donnell, A.F., Tiong, S., Nash, D. and Clark, D.V. The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway. Genetics 154 (2000) 1239–1253. [PMID: 10757766]
6.  Nelson, S.W., Binkowski, D.J., Honzatko, R.B. and Fromm, H.J. Mechanism of action of Escherichia coli phosphoribosylaminoimidazolesuccinocarboxamide synthetase. Biochemistry 44 (2005) 766–774. [PMID: 15641804]
[EC 6.3.2.6 created 1961, modified 2000, modified 2006]
 
 
EC 6.3.2.7     
Accepted name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + L-lysine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-L-lysine
Other name(s): MurE synthetase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine synthetase; uridine diphospho-N-acetylmuramoylalanyl-D-glutamyllysine synthetase; UPD-MurNAc-L-Ala-D-Glu:L-Lys ligase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine γ-ligase (ADP-forming)
Systematic name: UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate:L-lysine γ-ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria. This enzyme adds lysine in some Gram-positive organisms; in others and in Gram-negative organisms EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase) adds 2,6-diaminopimelate instead.
References:
1.  Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. I. Enzymatic addition of L-alanine, D-glutamic acid, and L-lysine. J. Biol. Chem. 237 (1962) 2689–2695.
2.  van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503–519. [PMID: 11699883]
[EC 6.3.2.7 created 1961, modified 2002]
 
 
EC 6.3.2.8     
Accepted name: UDP-N-acetylmuramate—L-alanine ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramate + L-alanine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanine
Other name(s): MurC synthetase; UDP-N-acetylmuramoyl-L-alanine synthetase; uridine diphospho-N-acetylmuramoylalanine synthetase; UDP-N-acetylmuramoylalanine synthetase; L-alanine-adding enzyme; UDP-acetylmuramyl-L-alanine synthetase; UDPMurNAc-L-alanine synthetase; L-Ala ligase; uridine diphosphate N-acetylmuramate:L-alanine ligase; uridine 5′-diphosphate-N-acetylmuramyl-L-alanine synthetase; uridine-diphosphate-N-acetylmuramate:L-alanine ligase; UDP-MurNAc:L-alanine ligase; alanine-adding enzyme; UDP-N-acetylmuramyl:L-alanine ligase; UDP-N-acetylmuramate:L-alanine ligase (ADP-forming)
Systematic name: UDP-N-acetyl-α-D-muramate:L-alanine ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria.
References:
1.  Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. I. Enzymatic addition of L-alanine, D-glutamic acid, and L-lysine. J. Biol. Chem. 237 (1962) 2689–2695.
2.  Nathenson, S.G., Strominger, J.L. and Ito, E. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. IV. Purification and properties of D-glutamic acid-adding enzyme. J. Biol. Chem. 239 (1964) 1773–1776. [PMID: 14213349]
3.  van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503–519. [PMID: 11699883]
[EC 6.3.2.8 created 1965, modified 2002]
 
 
EC 6.3.2.9     
Accepted name: UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanine + D-glutamate = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate
Other name(s): MurD synthetase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamate synthetase; uridine diphospho-N-acetylmuramoylalanyl-D-glutamate synthetase; D-glutamate-adding enzyme; D-glutamate ligase; UDP-Mur-NAC-L-Ala:D-Glu ligase; UDP-N-acetylmuramoyl-L-alanine:glutamate ligase (ADP-forming); UDP-N-acetylmuramoylalanine—D-glutamate ligase; UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (ADP-forming)
Systematic name: UDP-N-acetyl-α-D-muramoyl-L-alanine:D-glutamate ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria.
References:
1.  Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. I. Enzymatic addition of L-alanine, D-glutamic acid, and L-lysine. J. Biol. Chem. 237 (1962) 2689–2695.
2.  van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503–519. [PMID: 11699883]
[EC 6.3.2.9 created 1965, modified 2002]
 
 
EC 6.3.2.10     
Accepted name: UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase
Reaction: ATP + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-L-lysine + D-alanyl-D-alanine = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-L-lysyl-D-alanyl-D-alanine
Other name(s): MurF synthetase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine synthetase; UDP-N-acetylmuramoylalanyl-D-glutamyl-lysine-D-alanyl-D-alanine ligase; uridine diphosphoacetylmuramoylpentapeptide synthetase; UDPacetylmuramoylpentapeptide synthetase; UDP-MurNAc-L-Ala-D-Glu-L-Lys:D-Ala-D-Ala ligase
Systematic name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine:D-alanyl-D-alanine ligase (ADP-forming)
Comments: Involved with EC 6.3.2.4 (D-alanine—D-alanine ligase), EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate—L-alanine ligase) and EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine—D-glutamate ligase) in the synthesis of a cell-wall peptide (click here) for diagram. This enzyme also catalyses the reaction when the C-terminal residue of the tripeptide is meso-2,4-diaminoheptanedioate (acylated at its L-centre), linking the D-Ala-D-Ala to the carboxy group of the L-centre. This activity was previously attributed to EC 6.3.2.15, which has since been deleted.
References:
1.  Ito, E. and Strominger, J.L. Enzymatic synthesis of the peptide in bacterial uridine nucleotides. II. Enzymatic synthesis and addition of D-alanyl-D-alanine. J. Biol. Chem. 237 (1962) 2696–2703.
2.  van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503–519. [PMID: 11699883]
[EC 6.3.2.10 created 1965, modified 2002]
 
 
EC 6.3.2.11     
Accepted name: carnosine synthase
Reaction: ATP + L-histidine + β-alanine = ADP + phosphate + carnosine
Glossary: carnosine = N-β-alanyl-L-histidine
Other name(s): carnosine synthetase; carnosine-anserine synthetase; homocarnosine-carnosine synthetase; carnosine-homocarnosine synthetase; L-histidine:β-alanine ligase (AMP-forming) (incorrect)
Systematic name: L-histidine:β-alanine ligase (ADP-forming)
Comments: This enzyme was thought to form AMP [1,2], but studies with highly purified enzyme proved that it forms ADP [4]. Carnosine is a dipeptide that is present at high concentrations in skeletal muscle and the olfactory bulb of vertebrates [3]. It is also found in the skeletal muscle of some invertebrates. The enzyme can also catalyse the formation of homocarnosine from 4-aminobutanoate and L-histidine, with much lower activity [4].
References:
1.  Kalyankar, G.D. and Meister, A. Enzymatic synthesis of carnosine and related β-alanyl and γ-aminobutyryl peptides. J. Biol. Chem. 234 (1959) 3210–3218. [PMID: 14404206]
2.  Stenesh, J.J. and Winnick, T. Carnosine-anserine synthetase of muscle. 4. Partial purification of the enzyme and further studies of β-alanyl peptide synthesis. Biochem. J. 77 (1960) 575–581. [PMID: 16748858]
3.  Crush, K.G. Carnosine and related substances in animal tissues. Comp. Biochem. Physiol. 34 (1970) 3–30. [PMID: 4988625]
4.  Drozak, J., Veiga-da-Cunha, M., Vertommen, D., Stroobant, V. and Van Schaftingen, E. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J. Biol. Chem. 285 (2010) 9346–9356. [PMID: 20097752]
[EC 6.3.2.11 created 1965, modified 2010]
 
 
EC 6.3.2.12     
Accepted name: dihydrofolate synthase
Reaction: ATP + 7,8-dihydropteroate + L-glutamate = ADP + phosphate + 7,8-dihydropteroylglutamate
Other name(s): dihydrofolate synthetase; 7,8-dihydrofolate synthetase; H2-folate synthetase; 7,8-dihydropteroate:L-glutamate ligase (ADP); dihydropteroate:L-glutamate ligase (ADP-forming); DHFS
Systematic name: 7,8-dihydropteroate:L-glutamate ligase (ADP-forming)
Comments: In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.17, tetrahydrofolate synthase [2], the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates. In contrast, the activities are located on separate proteins in most eukaryotes studied to date [3]. This enzyme is reponsible for attaching the first glutamate residue to dihydropteroate to form dihydrofolate and is present only in those organisms that have the ability to synthesize tetrahydrofolate de novo, e.g. plants, most bacteria, fungi and protozoa [3].
References:
1.  Griffin, M.J. and Brown, G.M. The biosynthesis of folic acid. III. Enzymatic formation of dihydrofolic acid from dihydropteroic acid and of tetrahydropteroylpolyglutamic acid compounds from tetrahydrofolic acid. J. Biol. Chem. 239 (1964) 310–316. [PMID: 14114858]
2.  Bognar, A.L., Osborne, C., Shane, B., Singer, S.C. and Ferone, R. Folylpoly-γ-glutamate synthetase-dihydrofolate synthetase. Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product. J. Biol. Chem. 260 (1985) 5625–5630. [PMID: 2985605]
3.  Ravanel, S., Cherest, H., Jabrin, S., Grunwald, D., Surdin-Kerjan, Y., Douce, R. and Rébeillé, F. Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 98 (2001) 15360–15365. [PMID: 11752472]
4.  Cherest, H., Thomas, D. and Surdin-Kerjan, Y. Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. J. Biol. Chem. 275 (2000) 14056–14063. [PMID: 10799479]
5.  Cossins, E.A. and Chen, L. Folates and one-carbon metabolism in plants and fungi. Phytochemistry 45 (1997) 437–452. [PMID: 9190084]
[EC 6.3.2.12 created 1972, modified 2005]
 
 
EC 6.3.2.13     
Accepted name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—2,6-diaminopimelate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate
Other name(s): MurE synthetase [ambiguous]; UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diamino-heptanedioate ligase (ADP-forming); UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelate synthetase; UDP-N-acetylmuramoylalanyl-D-glutamate—2,6-diaminopimelate ligase; UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diaminoheptanedioate γ-ligase (ADP-forming)
Systematic name: UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate:meso-2,6-diaminoheptanedioate γ-ligase (ADP-forming)
Comments: Involved in the synthesis of a cell-wall peptide in bacteria. This enzyme adds diaminopimelate in Gram-negative organisms and in some Gram-positive organisms; in others EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase) adds lysine instead. It is the amino group of the L-centre of the diaminopimelate that is acylated.
References:
1.  Mizuno, Y. and Ito, E. Purification and properties of uridine diphosphate N-acetylmuramyl-L-alanyl-D-glutamate:meso-2,6-diaminopimelate ligase. J. Biol. Chem. 243 (1968) 2665–2672. [PMID: 4967958]
2.  van Heijenoort, J. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18 (2001) 503–519. [PMID: 11699883]
[EC 6.3.2.13 created 1972, modified 2002, modified 2010]
 
 
EC 6.3.2.14     
Accepted name: enterobactin synthase
Reaction: 6 ATP + 3 2,3-dihydroxybenzoate + 3 L-serine = enterobactin + 6 AMP + 6 diphosphate
Other name(s): N-(2,3-dihydroxybenzoyl)-serine synthetase; 2,3-dihydroxybenzoylserine synthetase; 2,3-dihydroxybenzoate—serine ligase
Systematic name: 2,3-dihydroxybenzoate:L-serine ligase
Comments: This enzyme complex catalyses the conversion of three molecules each of 2,3-dihydroxybenzoate and L-serine to form the siderophore enterobactin. In Escherichia coli the complex is formed by EntB (an aryl carrier protein that has to be activated by 4′-phosphopantetheine), EntD (a phosphopantetheinyl transferase that activates EntB), EntE (catalyses the ATP-dependent condensation of 2,3-dihydroxybenzoate and holo-EntB to form the covalently arylated form of EntB), and EntF (a four domain protein that catalyses the activation of L-serine by ATP, the condensation of the activated L-serine with the activated 2,3-dihydroxybenzoate, and the trimerization of three such moieties to a single enterobactin molecule).
References:
1.  Brot, N. and Goodwin, J. Regulation of 2,3-dihydroxybenzoylserine synthetase by iron. J. Biol. Chem. 243 (1968) 510–513. [PMID: 4966114]
2.  Rusnak, F., Faraci, W.S. and Walsh, C.T. Subcloning, expression, and purification of the enterobactin biosynthetic enzyme 2,3-dihydroxybenzoate-AMP ligase: demonstration of enzyme-bound (2,3-dihydroxybenzoyl)adenylate product. Biochemistry 28 (1989) 6827–6835. [PMID: 2531000]
3.  Rusnak, F., Liu, J., Quinn, N., Berchtold, G.A. and Walsh, C.T. Subcloning of the enterobactin biosynthetic gene entB: expression, purification, characterization, and substrate specificity of isochorismatase. Biochemistry 29 (1990) 1425–1435. [PMID: 2139796]
4.  Rusnak, F., Sakaitani, M., Drueckhammer, D., Reichert, J. and Walsh, C.T. Biosynthesis of the Escherichia coli siderophore enterobactin: sequence of the entF gene, expression and purification of EntF, and analysis of covalent phosphopantetheine. Biochemistry 30 (1991) 2916–2927. [PMID: 1826089]
5.  Gehring, A.M., Mori, I. and Walsh, C.T. Reconstitution and characterization of the Escherichia coli enterobactin synthetase from EntB, EntE, and EntF. Biochemistry 37 (1998) 2648–2659. [PMID: 9485415]
6.  Shaw-Reid, C.A., Kelleher, N.L., Losey, H.C., Gehring, A.M., Berg, C. and Walsh, C.T. Assembly line enzymology by multimodular nonribosomal peptide synthetases: the thioesterase domain of E. coli EntF catalyzes both elongation and cyclolactonization. Chem. Biol. 6 (1999) 385–400. [PMID: 10375542]
[EC 6.3.2.14 created 1972, modified 2012]
 
 
EC 6.3.2.15      
Deleted entry:  UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanine ligase. The activity observed is due to EC 6.3.2.10, UDP-N-acetylmuramoyl-tripeptide—D-alanyl-D-alanine ligase
[EC 6.3.2.15 created 1976, deleted 2002]
 
 
EC 6.3.2.16     
Accepted name: D-alanine—alanyl-poly(glycerolphosphate) ligase
Reaction: ATP + D-alanine + alanyl-poly(glycerolphosphate) = ADP + phosphate + D-alanyl-alanyl-poly(glycerolphosphate)
Other name(s): D-alanyl-alanyl-poly(glycerolphosphate) synthetase; D-alanine:membrane-acceptor ligase; D-alanylalanylpoly(phosphoglycerol) synthetase; D-alanyl-poly(phosphoglycerol) synthetase; D-alanine-membrane acceptor-ligase
Systematic name: D-alanine:alanyl-poly(glycerolphosphate) ligase (ADP-forming)
Comments: Involved in the synthesis of teichoic acids.
References:
1.  Reusch, V.M. and Neuhaus, F.C. D-Alanine:membrane acceptor ligase from Lactobacillus casei. J. Biol. Chem. 246 (1971) 6136–6143. [PMID: 4399593]
[EC 6.3.2.16 created 1976]
 
 
EC 6.3.2.17     
Accepted name: tetrahydrofolate synthase
Reaction: ATP + tetrahydropteroyl-[γ-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[γ-Glu]n+1
Other name(s): folylpolyglutamate synthase; folate polyglutamate synthetase; formyltetrahydropteroyldiglutamate synthetase; N10-formyltetrahydropteroyldiglutamate synthetase; folylpoly-γ-glutamate synthase; folylpolyglutamyl synthetase; folylpoly(γ-glutamate) synthase; folylpolyglutamate synthetase; FPGS; tetrahydrofolylpolyglutamate synthase; tetrahydrofolate:L-glutamate γ-ligase (ADP-forming); tetrahydropteroyl-[γ-Glu]n:L-glutamate γ-ligase (ADP-forming)
Systematic name: tetrahydropteroyl-γ-polyglutamate:L-glutamate γ-ligase (ADP-forming)
Comments: In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.12, dihydrofolate synthase [3], the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates (H4folate). In contrast, the activities are located on separate proteins in most eukaryotes studied to date [4]. In Arabidopsis thaliana, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes [4]. As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C1 metabolism. (reviewed in [5]). The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.
References:
1.  Cichowicz, D., Foo, S.K. and Shane, B. Folylpoly-γ-glutamate synthesis by bacteria and mammalian cells. Mol. Cell. Biochem. 39 (1981) 209–228. [PMID: 6458762]
2.  McGuire, J.J. and Bertino, J.R. Enzymatic synthesis and function of folylpolyglutamates. Mol. Cell. Biochem. 38 (1981) 19–48. [PMID: 7027025]
3.  Bognar, A.L., Osborne, C., Shane, B., Singer, S.C. and Ferone, R. Folylpoly-γ-glutamate synthetase-dihydrofolate synthetase. Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product. J. Biol. Chem. 260 (1985) 5625–5630. [PMID: 2985605]
4.  Ravanel, S., Cherest, H., Jabrin, S., Grunwald, D., Surdin-Kerjan, Y., Douce, R. and Rébeillé, F. Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 98 (2001) 15360–15365. [PMID: 11752472]
5.  Cossins, E.A. and Chen, L. Folates and one-carbon metabolism in plants and fungi. Phytochemistry 45 (1997) 437–452. [PMID: 9190084]
6.  Cherest, H., Thomas, D. and Surdin-Kerjan, Y. Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. J. Biol. Chem. 275 (2000) 14056–14063. [PMID: 10799479]
[EC 6.3.2.17 created 1984, modified 2003, modified 2005]
 
 
EC 6.3.2.18     
Accepted name: γ-glutamylhistamine synthase
Reaction: ATP + L-glutamate + histamine = products of ATP breakdown + Nα-γ-L-glutamylhistamine
Other name(s): γ-glutaminylhistamine synthetase; γ-GHA synthetase
Systematic name: L-glutamate:histamine ligase
References:
1.  Stein, C. and Weinreich, D. An in vitro characterization of γ-glutamylhistamine synthetase: a novel enzyme catalyzing histamine metabolism in the central nervous system of the marine mollusk, Aplysia californica. J. Neurochem. 38 (1982) 204–214. [PMID: 6125565]
[EC 6.3.2.18 created 1986]
 
 
EC 6.3.2.19      
Deleted entry: ubiquitin—protein ligase. The ubiquitinylation process is now known to be performed by several enzymes in sequence, starting with EC 6.2.1.45 (ubiquitin-activating enzyme E1) and followed by several transfer reactions, including those of EC 2.3.2.23 (E2 ubiquitin-conjugating enzyme) and EC 2.3.2.27 (RING-type E3 ubiquitin transferase)
[EC 6.3.2.19 created 1986, deleted 2015]
 
 
EC 6.3.2.20     
Accepted name: indoleacetate—lysine synthetase
Reaction: ATP + (indol-3-yl)acetate + L-lysine = ADP + phosphate + N6-[(indol-3-yl)acetyl]-L-lysine
Other name(s): indoleacetate:L-lysine ligase (ADP-forming)
Systematic name: (indol-3-yl)acetate:L-lysine ligase (ADP-forming)
References:
1.  Glass, N.L. and Kosuge, T. Cloning of the gene for indoleacetic acid-lysine synthetase from Pseudomonas syringae subsp. savastanoi. J. Bacteriol. 166 (1986) 598. [PMID: 3084452]
2.  Hutzinger, O. and Kosuge, T. Microbial synthesis and degradation of indole-3-acetic acid. 3. The isolation and characterization of indole-3-acetyl-ε-L-lysine. Biochemistry 7 (1968) 601–605. [PMID: 5644130]
[EC 6.3.2.20 created 1989]
 
 
EC 6.3.2.21      
Deleted entry: ubiquitin—calmodulin ligase. The reaction is performed by the sequential action of EC 6.2.1.45 (ubiquitin-activating enzyme E1), several ubiquitin transferases and finally by EC 2.3.2.27 [ubiquitin transferase RING E3 (calmodulin-selective)]
[EC 6.3.2.21 created 1990, deleted 2015]
 
 
EC 6.3.2.22      
Transferred entry: diphthine—ammonia ligase. Now EC 6.3.1.14, diphthine—ammonia ligase.
[EC 6.3.2.22 created 1990, deleted 2010]
 
 
EC 6.3.2.23     
Accepted name: homoglutathione synthase
Reaction: ATP + γ-L-glutamyl-L-cysteine + β-alanine = ADP + phosphate + γ-L-glutamyl-L-cysteinyl-β-alanine
Other name(s): homoglutathione synthetase; β-alanine specific hGSH synthetase
Systematic name: γ-L-glutamyl-L-cysteine:β-alanine ligase (ADP-forming)
Comments: Not identical with EC 6.3.2.3 glutathione synthase.
References:
1.  Macnicol, P.K. Homoglutathione and glutathione synthetases of legume seedlings - partial-purification and substrate-specificity. Plant Sci. 53 (1987) 229–235.
[EC 6.3.2.23 created 1990]
 
 
EC 6.3.2.24     
Accepted name: tyrosine—arginine ligase
Reaction: ATP + L-tyrosine + L-arginine = AMP + diphosphate + L-tyrosyl-L-arginine
Other name(s): tyrosyl-arginine synthase; kyotorphin synthase; kyotorphin-synthesizing enzyme; kyotorphin synthetase
Systematic name: L-tyrosine:L-arginine ligase (AMP-forming)
References:
1.  Ueda, H., Yoshihara, Y., Fukushima, N., Shiomi, H., Nakamura, A. and Takagi, H. Kyotorphin (tyrosine-arginine) synthetase in rat brain synaptosomes. J. Biol. Chem. 262 (1987) 8165–8173. [PMID: 3597366]
[EC 6.3.2.24 created 1992]
 
 
EC 6.3.2.25     
Accepted name: tubulin—tyrosine ligase
Reaction: ATP + detyrosinated α-tubulin + L-tyrosine = α-tubulin + ADP + phosphate
Systematic name: α-tubulin:L-tyrosine ligase (ADP-forming)
Comments: L-Tyrosine is linked via a peptide bond to the C-terminus of de-tyrosinated α-tubulin (des-Tyrω-α-tubulin). The enzyme is highly specific for α-tubulin and moderately specific for ATP and L-tyrosine. L-Phenylalanine and 3,4-dihydroxy-L-phenylalanine are transferred but with higher Km values.
References:
1.  Wehland, J., Schröder, H.C., Weber, K. Isolation and purification of tubulin-tyrosine ligase. Methods Enzymol. 134 (1986) 170–179. [PMID: 3821560]
2.  Rudiger, M., Wehland, J., Weber, K. The carboxy-terminal peptide of detyrosinated α tubulin provides a minimal system to study the substrate specificity of tubulin-tyrosine ligase. Eur. J. Biochem. 220 (1994) 309–320. [PMID: 7510228]
[EC 6.3.2.25 created 1999]
 
 
EC 6.3.2.26     
Accepted name: N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
Reaction: 3 ATP + L-2-aminohexanedioate + L-cysteine + L-valine + H2O = 3 AMP + 3 diphosphate + N-[L-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine
Other name(s): L-δ-(α-aminoadipoyl)-L-cysteinyl-D-valine synthetase; ACV synthetase; L-α-aminoadipyl-cysteinyl-valine synthetase;
Systematic name: L-2-aminohexanedioate:L-cysteine:L-valine ligase (AMP-forming, valine-inverting)
Comments: Requires Mg2+. The enzyme contains 4′-phosphopantetheine, which may be involved in the mechanism of the reaction. Forms part of the penicillin biosynthesis pathway (for pathway, click here).
References:
1.  Byford, M.F., Baldwin, J.E., Shiau, C.-Y. and Schofield, C.J. The mechanism of ACV synthetase. Chem. Rev. 97 (1997) 2631–2649. [PMID: 11851475]
2.  Theilgaard, H.B., Kristiansen, K.N., Henriksen, C.M. and Nielsen, J. Purification and characterization of δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase from Penicillium chrysogenum. Biochem. J. 327 (1997) 185–191. [PMID: 9355751]
[EC 6.3.2.26 created 2002]
 
 
EC 6.3.2.27      
Deleted entry: The activity is covered by two independent enzymes, EC 6.3.2.38 N2-citryl-N6-acetyl-N6-hydroxylysine synthase, and EC 6.3.2.39, aerobactin synthase
[EC 6.3.2.27 created 2002, modified 2006, deleted 2012]
 
 
EC 6.3.2.28      
Transferred entry: L-amino-acid α-ligase. Now EC 6.3.2.49, L-alanine-L-anticapsin ligase
[EC 6.3.2.28 created 2006, deleted 2015]
 
 
EC 6.3.2.29     
Accepted name: cyanophycin synthase (L-aspartate-adding)
Reaction: ATP + [L-Asp(4-L-Arg)]n + L-Asp = ADP + phosphate + [L-Asp(4-L-Arg)]n-L-Asp
Glossary: cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine}
Other name(s): CphA (ambiguous); CphA1 (ambiguous); CphA2 (ambiguous); cyanophycin synthetase (ambiguous); multi-L-arginyl-poly-L-aspartate synthase (ambiguous)
Systematic name: cyanophycin:L-aspartate ligase (ADP-forming)
Comments: Requires Mg2+ for activity. Both this enzyme and EC 6.3.2.30, cyanophycin synthase (L-arginine-adding), are required for the elongation of cyanophycin, which is a protein-like cell inclusion that is unique to cyanobacteria and acts as a temporary nitrogen store [2]. Both enzymes are found in the same protein but have different active sites [2,4]. Both L-Asp and L-Arg must be present before either enzyme will display significant activity [2].
References:
1.  Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Arch. Microbiol. 174 (2000) 297–306. [PMID: 11131019]
2.  Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its characterization with respect to substrate and primer specificity. Appl. Environ. Microbiol. 67 (2001) 2176–2182. [PMID: 11319097]
3.  Allen, M.M., Hutchison, F. and Weathers, P.J. Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. J. Bacteriol. 141 (1980) 687–693. [PMID: 6767688]
4.  Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W. and Volkmer-Engert, R. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur. J. Biochem. 267 (2000) 5561–5570. [PMID: 10951215]
5.  Ziegler, K., Deutzmann, R. and Lockau, W. Cyanophycin synthetase-like enzymes of non-cyanobacterial eubacteria: characterization of the polymer produced by a recombinant synthetase of Desulfitobacterium hafniense. Z. Naturforsch. [C] 57 (2002) 522–529. [PMID: 12132696]
6.  Ziegler, K., Diener, A., Herpin, C., Richter, R., Deutzmann, R. and Lockau, W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur. J. Biochem. 254 (1998) 154–159. [PMID: 9652408]
[EC 6.3.2.29 created 2007]
 
 
EC 6.3.2.30     
Accepted name: cyanophycin synthase (L-arginine-adding)
Reaction: ATP + [L-Asp(4-L-Arg)]n-L-Asp + L-Arg = ADP + phosphate + [L-Asp(4-L-Arg)]n+1
Glossary: cyanophycin = [L-Asp(4-L-Arg)]n = N-β-aspartylarginine = [L-4-(L-arginin-2-N-yl)aspartic acid]n = poly{N4-[(1S)-1-carboxy-4-guanidinobutyl]-L-asparagine}
Other name(s): CphA (ambiguous); CphA1 (ambiguous); CphA2 (ambiguous); cyanophycin synthetase (ambiguous); multi-L-arginyl-poly-L-aspartate synthase (ambiguous)
Systematic name: cyanophycin:L-arginine ligase (ADP-forming)
Comments: Requires Mg2+ for activity. Both this enzyme and EC 6.3.2.29, cyanophycin synthase (L-aspartate-adding), are required for the elongation of cyanophycin, which is a protein-like cell inclusion that is unique to cyanobacteria and acts as a temporary nitrogen store [2]. Both enzymes are found in the same protein but have different active sites [2,4]. Both L-Asp and L-Arg must be present before either enzyme will display significant activity [2]. Canavanine and lysine can be incoporated into the polymer instead of arginine [2].
References:
1.  Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Arch. Microbiol. 174 (2000) 297–306. [PMID: 11131019]
2.  Aboulmagd, E., Oppermann-Sanio, F.B. and Steinbüchel, A. Purification of Synechocystis sp. strain PCC6308 cyanophycin synthetase and its characterization with respect to substrate and primer specificity. Appl. Environ. Microbiol. 67 (2001) 2176–2182. [PMID: 11319097]
3.  Allen, M.M., Hutchison, F. and Weathers, P.J. Cyanophycin granule polypeptide formation and degradation in the cyanobacterium Aphanocapsa 6308. J. Bacteriol. 141 (1980) 687–693. [PMID: 6767688]
4.  Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W. and Volkmer-Engert, R. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur. J. Biochem. 267 (2000) 5561–5570. [PMID: 10951215]
5.  Ziegler, K., Deutzmann, R. and Lockau, W. Cyanophycin synthetase-like enzymes of non-cyanobacterial eubacteria: characterization of the polymer produced by a recombinant synthetase of Desulfitobacterium hafniense. Z. Naturforsch. [C] 57 (2002) 522–529. [PMID: 12132696]
6.  Ziegler, K., Diener, A., Herpin, C., Richter, R., Deutzmann, R. and Lockau, W. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin). Eur. J. Biochem. 254 (1998) 154–159. [PMID: 9652408]
[EC 6.3.2.30 created 2007]
 
 
EC 6.3.2.31     
Accepted name: coenzyme F420-0:L-glutamate ligase
Reaction: GTP + coenzyme F420-0 + L-glutamate = GDP + phosphate + coenzyme F420-1
Glossary: coenzyme F420 = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate
Other name(s): CofE-AF; MJ0768; CofE
Systematic name: L-glutamate:coenzyme F420-0 ligase (GDP-forming)
Comments: This protein catalyses the successive addition of two glutamate residues to cofactor F420 by two distinct and independent reactions. In the reaction described here the enzyme attaches a glutamate via its α-amine group to F420-0. In the second reaction (EC 6.3.2.34, coenzyme F420-1—γ-L-glutamate ligase) it catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate.
References:
1.  Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F420-0 in F420 coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771–9778. [PMID: 12911320]
2.  Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F420:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456–469. [PMID: 17669425]
[EC 6.3.2.31 created 2010]
 
 
EC 6.3.2.32     
Accepted name: coenzyme γ-F420-2:α-L-glutamate ligase
Reaction: ATP + coenzyme γ-F420-2 + L-glutamate = ADP + phosphate + coenzyme α-F420-3
Other name(s): MJ1001; CofF protein; γ-F420-2:α-L-glutamate ligase
Systematic name: L-glutamate:coenzyme γ-F420-2 (ADP-forming)
Comments: The enzyme caps the γ-glutamyl tail of the hydride carrier coenzyme F420 [1].
References:
1.  Li, H., Xu, H., Graham, D.E. and White, R.H. Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses. Proc. Natl. Acad. Sci. USA 100 (2003) 9785–9790. [PMID: 12909715]
[EC 6.3.2.32 created 2010]
 
 
EC 6.3.2.33     
Accepted name: tetrahydrosarcinapterin synthase
Reaction: ATP + tetrahydromethanopterin + L-glutamate = ADP + phosphate + 5,6,7,8-tetrahydrosarcinapterin
Other name(s): H4MPT:α-L-glutamate ligase; MJ0620; MptN protein
Systematic name: tetrahydromethanopterin:α-L-glutamate ligase (ADP-forming)
Comments: This enzyme catalyses the biosynthesis of 5,6,7,8-tetrahydrosarcinapterin, a modified form of tetrahydromethanopterin found in the Methanosarcinales. It does not require K+, and does not discriminate between ATP and GTP [1].
References:
1.  Li, H., Xu, H., Graham, D.E. and White, R.H. Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses. Proc. Natl. Acad. Sci. USA 100 (2003) 9785–9790. [PMID: 12909715]
[EC 6.3.2.33 created 2010]
 
 
EC 6.3.2.34     
Accepted name: coenzyme F420-1:γ-L-glutamate ligase
Reaction: GTP + coenzyme F420-1 + L-glutamate = GDP + phosphate + coenzyme γ-F420-2
Glossary: coenzyme F420 = N-(N-{O-[5-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-10-yl)-5-deoxy-L-ribityl-1-phospho]-(S)-lactyl}-γ-L-glutamyl)-L-glutamate
Other name(s): F420:γ-glutamyl ligase; CofE-AF; MJ0768; CofE
Systematic name: L-glutamate:coenzyme F420-1 ligase (GDP-forming)
Comments: This protein catalyses the successive addition of two glutamate residues to cofactor F420 by two distinct and independent reactions. In the first reaction (EC 6.3.2.31, coenzyme F420-0—L-glutamate ligase) the enzyme attaches a glutamate via its α-amine group to F420-0. In the second reaction, which is described here, the enzyme catalyses the addition of a second L-glutamate residue to the γ-carboxyl of the first glutamate.
References:
1.  Li, H., Graupner, M., Xu, H. and White, R.H. CofE catalyzes the addition of two glutamates to F420-0 in F420 coenzyme biosynthesis in Methanococcus jannaschii. Biochemistry 42 (2003) 9771–9778. [PMID: 12911320]
2.  Nocek, B., Evdokimova, E., Proudfoot, M., Kudritska, M., Grochowski, L.L., White, R.H., Savchenko, A., Yakunin, A.F., Edwards, A. and Joachimiak, A. Structure of an amide bond forming F420:γ-glutamyl ligase from Archaeoglobus fulgidus — a member of a new family of non-ribosomal peptide synthases. J. Mol. Biol. 372 (2007) 456–469. [PMID: 17669425]
[EC 6.3.2.34 created 2010]
 
 
EC 6.3.2.35     
Accepted name: D-alanine—D-serine ligase
Reaction: D-alanine + D-serine + ATP = D-alanyl-D-serine + ADP + phosphate
Other name(s): VanC; VanE; VanG
Systematic name: D-alanine:D-serine ligase (ADP-forming)
Comments: The product of this enzyme, D-alanyl-D-serine, can be incorporated into the peptidoglycan pentapeptide instead of the usual D-alanyl-D-alanine dipeptide, which is formed by EC 6.3.2.4, D-alanine—D-alanine ligase. The resulting peptidoglycan does not bind the glycopeptide antibiotics vancomycin and teicoplanin, conferring resistance on the bacteria.
References:
1.  Dutka-Malen, S., Molinas, C., Arthur, M. and Courvalin, P. Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine:D-alanine ligase-related protein necessary for vancomycin resistance. Gene 112 (1992) 53–58. [PMID: 1551598]
2.  Park, I.S., Lin, C.H. and Walsh, C.T. Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase. Proc. Natl. Acad. Sci. USA 94 (1997) 10040–10044. [PMID: 9294159]
3.  Fines, M., Perichon, B., Reynolds, P., Sahm, D.F. and Courvalin, P. VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis BM4405. Antimicrob. Agents Chemother. 43 (1999) 2161–2164. [PMID: 10471558]
4.  Depardieu, F., Bonora, M.G., Reynolds, P.E. and Courvalin, P. The vanG glycopeptide resistance operon from Enterococcus faecalis revisited. Mol. Microbiol. 50 (2003) 931–948. [PMID: 14617152]
5.  Watanabe, S., Kobayashi, N., Quinones, D., Hayakawa, S., Nagashima, S., Uehara, N. and Watanabe, N. Genetic diversity of the low-level vancomycin resistance gene vanC-2/vanC-3 and identification of a novel vanC subtype (vanC-4) in Enterococcus casseliflavus. Microb. Drug Resist. 15 (2009) 1–9. [PMID: 19216682]
[EC 6.3.2.35 created 2010]
 
 
EC 6.3.2.36     
Accepted name: 4-phosphopantoate—β-alanine ligase
Reaction: ATP + (R)-4-phosphopantoate + β-alanine = AMP + diphosphate + (R)-4′-phosphopantothenate
Other name(s): phosphopantothenate synthetase; TK1686 protein
Systematic name: (R)-4-phosphopantoate:β-alanine ligase (AMP-forming)
Comments: The conversion of (R)-pantoate to (R)-4′-phosphopantothenate is part of the pathway leading to biosynthesis of 4′-phosphopantetheine, an essential cofactor of coenzyme A and acyl-carrier protein. In bacteria and eukaryotes this conversion is performed by condensation with β-alanine, followed by phosphorylation (EC 6.3.2.1 [pantoate—β-alanine ligase] and EC 2.7.1.33 [pantothenate kinase], respectively). In archaea the order of these two steps is reversed, and phosphorylation precedes condensation with β-alanine. The two archaeal enzymes that catalyse this conversion are EC 2.7.1.169, pantoate kinase, and this enzyme.
References:
1.  Yokooji, Y., Tomita, H., Atomi, H. and Imanaka, T. Pantoate kinase and phosphopantothenate synthetase, two novel enzymes necessary for CoA biosynthesis in the Archaea. J. Biol. Chem. 284 (2009) 28137–28145. [PMID: 19666462]
[EC 6.3.2.36 created 2011]
 
 
EC 6.3.2.37     
Accepted name: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—D-lysine ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate + D-lysine = ADP + phosphate + UDP-N-acetyl-α-D-muramoyl-L-alanyl-γ-D-glutamyl-Nε-D-lysine
Glossary: muramic acid = 2-amino-3-O-[(R)-1-carboxyethyl]-2-deoxy-D-glucose
Other name(s): UDP-MurNAc-L-Ala-D-Glu:D-Lys ligase; D-lysine-adding enzyme
Systematic name: UDP-N-acetyl-α-D-muramoyl-L-alanyl-D-glutamate:D-lysine γ-ligase (ADP-forming)
Comments: Involved in the synthesis of cell-wall peptidoglycan. The D-lysine is attached to the peptide chain at the N6 position. The enzyme from Thermotoga maritima also performs the reaction of EC 6.3.2.7, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate—L-lysine ligase.
References:
1.  Boniface, A., Bouhss, A., Mengin-Lecreulx, D. and Blanot, D. The MurE synthetase from Thermotoga maritima is endowed with an unusual D-lysine adding activity. J. Biol. Chem. 281 (2006) 15680–15686. [PMID: 16595662]
[EC 6.3.2.37 created 2011, modified 2015]
 
 
EC 6.3.2.38     
Accepted name: N2-citryl-N6-acetyl-N6-hydroxylysine synthase
Reaction: 2 ATP + citrate + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine
Other name(s): Nα-citryl-Nε-acetyl-Nε-hydroxylysine synthase; iucA (gene name)
Systematic name: citrate:N6-acetyl-N6-hydroxy-L-lysine ligase (ADP-forming)
Comments: Requires Mg2+. Aerobactin is one of a group of high-affinity iron chelators known as siderophores and is produced under conditions of iron deprivation [5]. It is a dihydroxamate comprising two molecules of N6-acetyl-N6-hydroxy-L-lysine and one molecule of citrate. This enzyme catalyses the first of two synthase reactions to link N6-acetyl-N6-hydroxy-L-lysine and citrate [4,5].
References:
1.  Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443.
2.  Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [PMID: 4313071]
3.  Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101.
4.  de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [PMID: 2935523]
5.  Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [PMID: 15719346]
[EC 6.3.2.38 created 2012]
 
 
EC 6.3.2.39     
Accepted name: aerobactin synthase
Reaction: 2 ATP + N2-citryl-N6-acetyl-N6-hydroxy-L-lysine + N6-acetyl-N6-hydroxy-L-lysine + H2O = 2 ADP + 2 phosphate + aerobactin
Other name(s): iucC (gene name)
Systematic name: N2-citryl-N6-acetyl-N6-hydroxy-L-lysine:N6-acetyl-N6-hydroxy-L-lysine ligase (ADP-forming)
Comments: Requires Mg2+. Aerobactin is one of a group of high-affinity iron chelators known as siderophores and is produced under conditions of iron deprivation [6]. It is a dihydroxamate comprising two molecules of N6-acetyl-N6-hydroxy-L-lysine and one molecule of citric acid. This enzyme catalyses the second of two synthase reactions to link N6-acetyl-N6-hydroxy-L-lysine and citrate [3,4,5].
References:
1.  Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443.
2.  Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [PMID: 4313071]
3.  Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101.
4.  de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [PMID: 2935523]
5.  de Lorenzo, V. and Neilands, J.B. Characterization of iucA and iucC genes of the aerobactin system of plasmid ColV-K30 in Escherichia coli. J. Bacteriol. 167 (1986) 350–355. [PMID: 3087960]
6.  Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [PMID: 15719346]
[EC 6.3.2.39 created 2012]
 
 
EC 6.3.2.40     
Accepted name: cyclopeptine synthase
Reaction: 2 ATP + S-adenosyl-L-methionine + anthranilate + L-phenylalanine = cyclopeptine + 2 AMP + 2 diphosphate + S-adenosyl-L-homocysteine
Glossary: cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
Systematic name: S-adenosyl-L-methionine:anthranilate:L-phenylalanine ligase (cyclopeptine forming)
Comments: Cyclopeptine synthase is the key enzyme of benzodiazepine alkaloid biosynthesis in the fungus Penicillium cyclopium. The enzyme is a non-ribosomal peptide synthase.
References:
1.  Lerbs, W. and Luckner, M. Cyclopeptine synthetase activity in surface cultures of Penicillium cyclopium. J. Basic Microbiol. 25 (1985) 387–391. [PMID: 2995633]
2.  Gerlach, M, Schwelle, N., Lerbs, W. and Luckner, M. Enzymatic synthesis of cyclopeptine intermediates in Penicillium cyclopium. Phytochemistry 24 (1985) 1935–1939.
[EC 6.3.2.40 created 2013]
 
 
EC 6.3.2.41     
Accepted name: N-acetylaspartylglutamate synthase
Reaction: ATP + N-acetyl-L-aspartate + L-glutamate = ADP + phosphate + N-acetyl-L-aspartyl-L-glutamate
Other name(s): N-acetylaspartylglutamate synthetase; NAAG synthetase; NAAGS; RIMKLA (gene name) (ambiguous); RIMKLB (gene name) (ambiguous)
Systematic name: N-acetyl-L-aspartate:L-glutamate ligase (ADP, N-acetyl-L-aspartyl-L-glutamate-forming)
Comments: The enzyme, found in animals, produces the neurotransmitter N-acetyl-L-aspartyl-L-glutamate. One isoform also has the activity of EC 6.3.1.17, β-citrylglutamate synthase [2], while another isoform has the activity of EC 6.3.2.42, N-acetylaspartylglutamylglutamate synthase [3].
References:
1.  Becker, I., Lodder, J., Gieselmann, V. and Eckhardt, M. Molecular characterization of N-acetylaspartylglutamate synthetase. J. Biol. Chem. 285 (2010) 29156–29164. [PMID: 20643647]
2.  Collard, F., Stroobant, V., Lamosa, P., Kapanda, C.N., Lambert, D.M., Muccioli, G.G., Poupaert, J.H., Opperdoes, F. and Van Schaftingen, E. Molecular identification of N-acetylaspartylglutamate synthase and β-citrylglutamate synthase. J. Biol. Chem. 285 (2010) 29826–29833. [PMID: 20657015]
3.  Lodder-Gadaczek, J., Becker, I., Gieselmann, V., Wang-Eckhardt, L. and Eckhardt, M. N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate. J. Biol. Chem. 286 (2011) 16693–16706. [PMID: 21454531]
[EC 6.3.2.41 created 2014]
 
 
EC 6.3.2.42     
Accepted name: N-acetylaspartylglutamylglutamate synthase
Reaction: 2 ATP + N-acetyl-L-aspartate + 2 L-glutamate = 2 ADP + 2 phosphate + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate
Other name(s): N-acetylaspartylglutamylglutamate synthetase; NAAG(2) synthase; NAAG synthetase II; NAAGS-II; RIMKLA (gene name) (ambiguous)
Systematic name: N-acetyl-L-aspartate:L-glutamate ligase (ADP, N-acetyl-L-aspartyl-L-glutamyl-L-glutamate-forming)
Comments: The enzyme, found in mammals, also has the activity of EC 6.3.2.41, N-acetylaspartylglutamate synthase.
References:
1.  Lodder-Gadaczek, J., Becker, I., Gieselmann, V., Wang-Eckhardt, L. and Eckhardt, M. N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate. J. Biol. Chem. 286 (2011) 16693–16706. [PMID: 21454531]
[EC 6.3.2.42 created 2014]
 
 
EC 6.3.2.43     
Accepted name: [lysine-biosynthesis-protein LysW]—L-2-aminoadipate ligase
Reaction: ATP + [lysine-biosynthesis-protein LysW]-C-terminal-L-glutamate + L-2-aminoadipate = ADP + phosphate + [lysine-biosynthesis-protein LysW]-C-terminal-γ-(L-2-aminoadip-2-yl)-L-glutamate
Other name(s): α-aminoadipate-lysW ligase lysX (gene name); LysX (ambiguous); AAA—LysW ligase
Systematic name: [lysine-biosynthesis-protein LysW]-C-terminal-L-glutamate:L-2-aminoadipate ligase (ADP-forming)
Comments: The enzymes from the thermophilic bacterium Thermus thermophilus and the thermophilic archaea Sulfolobus acidocaldarius and Sulfolobus tokodaii protect the amino group of L-2-aminoadipate by conjugation to the carrier protein LysW. This reaction is part of the lysine biosynthesis pathway in these organisms.
References:
1.  Vassylyeva, M.N., Sakai, H., Matsuura, T., Sekine, S., Nishiyama, M., Terada, T., Shirouzu, M., Kuramitsu, S., Vassylyev, D.G. and Yokoyama, S. Cloning, expression, purification, crystallization and initial crystallographic analysis of the lysine-biosynthesis LysX protein from Thermus thermophilus HB8. Acta Crystallogr. D Biol. Crystallogr. 59 (2003) 1651–1652. [PMID: 12925802]
2.  Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673–679. [PMID: 19620981]
3.  Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277–283. [PMID: 23434852]
[EC 6.3.2.43 created 2014]
 
 
EC 6.3.2.44     
Accepted name: pantoate—β-alanine ligase (ADP-forming)
Reaction: ATP + (R)-pantoate + β-alanine = ADP + phosphate + (R)-pantothenate
Glossary: (R)-pantoate = (2R)-2,4-dihydroxy-3,3-dimethylbutanoate
(R)-pantothenate = 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoate
Other name(s): pantothenate synthetase (ambiguous); pantoate—β-alanine ligase (ambiguous)
Systematic name: (R)-pantoate:β-alanine ligase (ADP-forming)
Comments: The enzyme, characterized from the archaeon Methanosarcina mazei, is involved in the biosynthesis of pantothenate. It is different from EC 6.3.2.1, the AMP-forming pantoate-β-alanine ligase found in bacteria and eukaryota.
References:
1.  Ronconi, S., Jonczyk, R. and Genschel, U. A novel isoform of pantothenate synthetase in the Archaea. FEBS J. 275 (2008) 2754–2764. [PMID: 18422645]
[EC 6.3.2.44 created 2014]
 
 
EC 6.3.2.45     
Accepted name: UDP-N-acetylmuramate—L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase
Reaction: ATP + UDP-N-acetyl-α-D-muramate + L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate
Glossary: meso-2,6-diaminoheptanedioate = meso-2,6-diaminopimelate
Other name(s): murein peptide ligase; Mpl; yjfG (gene name); UDP-MurNAc:L-Ala-γ-D-Glu-meso-A2pm ligase; UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase
Systematic name: UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioate ligase2015
Comments: The enzyme catalyses the reincorporation into peptidoglycan of the tripeptide L-alanyl-γ-D-glutamyl-2,6-meso-diaminoheptanedioate released during the maturation and constant remodeling of this bacterial cell wall polymer that occur during cell growth and division. The enzyme can also use the tetrapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanine or the pentapeptide L-alanyl-γ-D-glutamyl-meso-2,6-diaminoheptanedioyl-D-alanyl-D-alanine in vivo and in vitro. Requires Mg2+.
References:
1.  Mengin-Lecreulx, D., van Heijenoort, J. and Park, J.T. Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan. J. Bacteriol. 178 (1996) 5347–5352. [PMID: 8808921]
2.  Herve, M., Boniface, A., Gobec, S., Blanot, D. and Mengin-Lecreulx, D. Biochemical characterization and physiological properties of Escherichia coli UDP-N-acetylmuramate:L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase. J. Bacteriol. 189 (2007) 3987–3995. [PMID: 17384195]
[EC 6.3.2.45 created 2014]
 
 
EC 6.3.2.46     
Accepted name: fumarate—(S)-2,3-diaminopropanoate ligase
Reaction: ATP + fumarate + L-2,3-diaminopropanoate = AMP + diphosphate + N3-fumaroyl-L-2,3-diaminopropanoate
Glossary: N3-fumaroyl-L-2,3-diaminopropanoate = (2E)-4-{[(2S)-2-amino-2-carboxyethyl]amino}-4-oxobut-2-enoate
L-2,3-diaminopropanoate = (S)-2,3-diaminopropanoate
Other name(s): DdaG; fumarate:(S)-2,3-diaminopropanoate ligase (AMP-forming)
Systematic name: fumarate:L-2,3-diaminopropanoate ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Enterobacter agglomerans, is involved in biosynthesis of dapdiamide tripeptide antibiotics, a family of fumaramoyl- and epoxysuccinamoyl-peptides named for the presence of an L-2,3-diaminopropanoate (DAP) moiety and two amide linkages in their scaffold.
References:
1.  Hollenhorst, M.A., Clardy, J. and Walsh, C.T. The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics. Biochemistry 48 (2009) 10467–10472. [PMID: 19807062]
[EC 6.3.2.46 created 2015]
 
 
EC 6.3.2.47     
Accepted name: dapdiamide synthase
Reaction: (1) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-valine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-valine
(2) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-isoleucine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-isoleucine
(3) ATP + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine + L-leucine = ADP + phosphate + 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-leucine
(4) ATP + 3-({[(2R,3R)-3-carbamoyloxiran-2-yl]carbonyl}amino)-L-alanine + L-valine = ADP + phosphate + 3-({[(2R,3R)-3-carbamoyloxiran-2-yl]carbonyl}amino)-L-alanyl-L-valine
Glossary: dapdiamide A = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-valine
dapdiamide B = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-isoleucine
dapdiamide C = 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanyl-L-leucine
Other name(s): DdaF; dapdiamide A synthase
Systematic name: 3-{[(2E)-4-amino-4-oxobut-2-enoyl]amino}-L-alanine:L-valine ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Pantoea agglomerans, is involved in biosynthesis of dapdiamide tripeptide antibiotics, a family of fumaramoyl- and epoxysuccinamoyl-peptides named for the presence of an (S)-2,3-diaminopropanoate (DAP) moiety and two amide linkages in their scaffold.
References:
1.  Hollenhorst, M.A., Clardy, J. and Walsh, C.T. The ATP-dependent amide ligases DdaG and DdaF assemble the fumaramoyl-dipeptide scaffold of the dapdiamide antibiotics. Biochemistry 48 (2009) 10467–10472. [PMID: 19807062]
2.  Hollenhorst, M.A., Bumpus, S.B., Matthews, M.L., Bollinger, J.M., Jr., Kelleher, N.L. and Walsh, C.T. The nonribosomal peptide synthetase enzyme DdaD tethers N(β)-fumaramoyl-L-2,3-diaminopropionate for Fe(II)/α-ketoglutarate-dependent epoxidation by DdaC during dapdiamide antibiotic biosynthesis. J. Am. Chem. Soc. 132 (2010) 15773–15781. [PMID: 20945916]
[EC 6.3.2.47 created 2015, modified 2016]
 
 
EC 6.3.2.48     
Accepted name: L-arginine-specific L-amino acid ligase
Reaction: ATP + L-arginine + an L-amino acid = ADP + phosphate + an L-arginyl-L-amino acid
Other name(s): RizA; L-amino acid ligase RizA
Systematic name: L-arginine:L-amino acid ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Bacillus subtilis, requires Mn2+ for activity. It shows strict substrate specificity toward L-arginine as the first (N-terminal) amino acid of the product. The second amino acid could be any standard protein-building amino acid except for L-proline.
References:
1.  Kino, K., Kotanaka, Y., Arai, T. and Yagasaki, M. A novel L-amino acid ligase from Bacillus subtilis NBRC3134, a microorganism producing peptide-antibiotic rhizocticin. Biosci. Biotechnol. Biochem. 73 (2009) 901–907. [PMID: 19352016]
[EC 6.3.2.48 created 2015]
 
 
EC 6.3.2.49     
Accepted name: L-alanine—L-anticapsin ligase
Reaction: ATP + L-alanine + L-anticapsin = ADP + phosphate + bacilysin
Glossary: L-anticapsin = 3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]hept-2-yl]-L-alanine
bacilysin = L-alanyl-3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]hept-2-yl]-L-alanine
Other name(s): BacD; alanine-anticapsin ligase; L-Ala-L-anticapsin ligase; ywfE (gene name)
Systematic name: L-alanine:L-anticapsin ligase (ADP-forming)
Comments: The enzyme, characterized from the bacterium Bacillus subtilis, is involved in the biosynthesis of the nonribosomally synthesized dipeptide antibiotic bacilysin, composed of L-alanine and L-anticapsin. The enzyme requires Mg2+ or Mn2+ for activity, and has a broad substrate specificity in vitro [1].
References:
1.  Tabata, K., Ikeda, H. and Hashimoto, S. ywfE in Bacillus subtilis codes for a novel enzyme, L-amino acid ligase. J. Bacteriol. 187 (2005) 5195–5202. [PMID: 16030213]
2.  Tsuda, T., Suzuki, T. and Kojima, S. Crystallization and preliminary X-ray diffraction analysis of Bacillus subtilis YwfE, an L-amino-acid ligase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 68 (2012) 203–206. [PMID: 22298000]
3.  Shomura, Y., Hinokuchi, E., Ikeda, H., Senoo, A., Takahashi, Y., Saito, J., Komori, H., Shibata, N., Yonetani, Y. and Higuchi, Y. Structural and enzymatic characterization of BacD, an L-amino acid dipeptide ligase from Bacillus subtilis. Protein Sci. 21 (2012) 707–716. [PMID: 22407814]
4.  Parker, J.B. and Walsh, C.T. Action and timing of BacC and BacD in the late stages of biosynthesis of the dipeptide antibiotic bacilysin. Biochemistry 52 (2013) 889–901. [PMID: 23317005]
[EC 6.3.2.49 created 2006 as EC 6.3.2.28, trasferred 2015 to EC 6.3.2.49]
 
 
EC 6.3.2.50     
Accepted name: tenuazonic acid synthetase
Reaction: ATP + L-isoleucine + acetoacetyl-CoA = AMP + diphosphate + tenuazonic acid + CoA
Glossary: tenuazonic acid = (5S)-3-acetyl-5-[(2S)-butan-2-yl]-4-hydroxy-1,5-dihydro-2H-pyrrol-2-one
Other name(s): TAS1 (gene name)
Systematic name: L-isoleucine:acetoacetyl-CoA ligase (tenuazonic acid-forming)
Comments: This fungal enzyme, isolated from Magnaporthe oryzae, is an non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) hybrid protein that consists of condensation (C), adenylation (A) and peptidyl-carrier protein (PCP) domains in the NRPS portion and a ketosynthase (KS) domain in the PKS portion. ATP is required for activation of isoleucine, which is then condensed with acetoacetyl-CoA. Cyclization and release from the enzyme are catalysed by the KS domain.
References:
1.  Yun, C.S., Motoyama, T. and Osada, H. Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS-PKS hybrid enzyme. Nat Commun 6:8758 (2015). [PMID: 26503170]
[EC 6.3.2.50 created 2017]
 
 
EC 6.3.2.51     
Accepted name: phosphopantothenate—cysteine ligase (ATP)
Reaction: ATP + (R)-4′-phosphopantothenate + L-cysteine = AMP + diphosphate + N-[(R)-4′-phosphopantothenoyl]-L-cysteine
Other name(s): phosphopantothenoylcysteine synthetase (ambiguous); PPCS (gene name)
Systematic name: (R)-4′-phosphopantothenate:L-cysteine ligase (ATP-utilizing)
Comments: A key enzyme in the production of coenzyme A. The eukaryotic enzyme requires ATP, in contrast to the bacterial enzyme, EC 6.3.2.5, phosphopantothenate—cysteine ligase, which requires CTP.
References:
1.  Daugherty, M. Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. J. Biol. Chem. 277 (2002) 21431–21439. [PMID: 11923312]
2.  Manoj, N., Strauss, E., Begley, T.P. and Ealick, S.E. Structure of human phosphopantothenoylcysteine synthetase at 2.3 Å Resolution. Structure 11 (2003) 927–936. [PMID: 12906824]
3.  Kupke, T., Hernandez-Acosta, P. and Culianez-Macia, F.A. 4′-phosphopantetheine and coenzyme A biosynthesis in plants. J. Biol. Chem. 278 (2003) 38229–38237. [PMID: 12860978]
[EC 6.3.2.51 created 2017]
 
 
EC 6.3.2.52     
Accepted name: jasmonoyl—L-amino acid synthetase
Reaction: ATP + jasmonate + an L-amino acid = AMP + diphosphate + a jasmonoyl-L-amino acid
Other name(s): JAR1 (gene name); JAR4 (gene name); JAR6 (gene name)
Systematic name: jasmonate:L-amino acid ligase
Comments: Two jasmonoyl-L-amino acid synthetases have been described from Nicotiana attenuata [3] and one from Arabidopsis thaliana [1]. The N. attenuata enzymes generate jasmonoyl-L-isoleucine, jasmonoyl-L-leucine, and jasmonoyl-L-valine. The enzyme from A. thaliana could catalyse the addition of many different amino acids to jasmonate in vitro [1,4,5]. While the abundant form of jasmonate in plants is (–)-jasmonate, the active form of jasmonoyl-L-isoleucine is (+)-7-iso-jasmonoyl-L-isoleucine.
References:
1.  Staswick, P.E. and Tiryaki, I. The oxylipin signal jasmonic acid is activated by an enzyme that conjugates it to isoleucine in Arabidopsis. Plant Cell 16 (2004) 2117–2127. [PMID: 15258265]
2.  Kang, J.H., Wang, L., Giri, A. and Baldwin, I.T. Silencing threonine deaminase and JAR4 in Nicotiana attenuata impairs jasmonic acid-isoleucine-mediated defenses against Manduca sexta. Plant Cell 18 (2006) 3303–3320. [PMID: 17085687]
3.  Wang, L., Halitschke, R., Kang, J.H., Berg, A., Harnisch, F. and Baldwin, I.T. Independently silencing two JAR family members impairs levels of trypsin proteinase inhibitors but not nicotine. Planta 226 (2007) 159–167. [PMID: 17273867]
4.  Guranowski, A., Miersch, O., Staswick, P.E., Suza, W. and Wasternack, C. Substrate specificity and products of side-reactions catalyzed by jasmonate:amino acid synthetase (JAR1). FEBS Lett. 581 (2007) 815–820. [PMID: 17291501]
5.  Suza, W.P. and Staswick, P.E. The role of JAR1 in jasmonoyl-L-isoleucine production during Arabidopsis wound response. Planta 227 (2008) 1221–1232. [PMID: 18247047]
[EC 6.3.2.52 created 2018]
 
 
EC 6.3.3.1     
Accepted name: phosphoribosylformylglycinamidine cyclo-ligase
Reaction: ATP + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole
Other name(s): phosphoribosylaminoimidazole synthetase; AIR synthetase; 5′-aminoimidazole ribonucleotide synthetase; 2-(formamido)-1-N-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming)
Systematic name: 2-(formamido)-N1-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming)
References:
1.  Levenberg, B. and Buchanan, J.M. Properties of the purines. XII. Structure, enzymatic synthesis, and metabolism of 5-aminoimidazole ribotide. J. Biol. Chem. 224 (1957) 1005–1018. [PMID: 13405929]
2.  Levenberg, B. and Buchanan, J.M. Biosynthesis of the purines. XIII. Structure, enzymatic synthesis, and metabolism of (α-N-formyl)-glycinamidine ribotide. J. Biol. Chem. 224 (1957) 1018–1027. [PMID: 13405930]
[EC 6.3.3.1 created 1961, modified 2000]
 
 
EC 6.3.3.2     
Accepted name: 5-formyltetrahydrofolate cyclo-ligase
Reaction: ATP + 5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate
Other name(s): 5,10-methenyltetrahydrofolate synthetase; formyltetrahydrofolic cyclodehydrase; 5-formyltetrahydrofolate cyclodehydrase
Systematic name: 5-formyltetrahydrofolate cyclo-ligase (ADP-forming)
References:
1.  Greenberg, D.M., Wynston, L.K. and Nagabhushanan, A. Further studies on N5-formyltetrahydrofolic acid cyclodehydrase. Biochemistry 4 (1965) 1872–1878.
[EC 6.3.3.2 created 1972]
 
 
EC 6.3.3.3     
Accepted name: dethiobiotin synthase
Reaction: ATP + 7,8-diaminononanoate + CO2 = ADP + phosphate + dethiobiotin
Other name(s): desthiobiotin synthase
Systematic name: 7,8-diaminononanoate:carbon-dioxide cyclo-ligase (ADP-forming)
Comments: CTP has half the activity of ATP.
References:
1.  Krell, K. and Eisenberg, M.A. The purification and properties of dethiobiotin synthetase. J. Biol. Chem. 245 (1970) 6558–6566. [PMID: 4921568]
2.  Yang, H.-C., Tani, Y. and Ogata, K. Synthesis of biotin vitamers from biotin diaminocarboxylic acid or 7,8-diaminopelargonic acid by a purified enzyme of Pseudomonas graveolens. Agric. Biol. Chem. 34 (1970) 1748–1750.
[EC 6.3.3.3 created 1976]
 
 
EC 6.3.3.4     
Accepted name: (carboxyethyl)arginine β-lactam-synthase
Reaction: ATP + L-N2-(2-carboxyethyl)arginine = AMP + diphosphate + deoxyamidinoproclavaminate
Other name(s): L-2-N-(2-carboxyethyl)arginine cyclo-ligase (AMP-forming)
Systematic name: L-N2-(2-carboxyethyl)arginine cyclo-ligase (AMP-forming)
Comments: Forms part of the pathway for the biosythesis of the β-lactamase inhibitor clavulanate in Streptomyces clavuligerus. It has been proposed [3] that L-N2-(2-carboxyethyl)arginine is first converted into an acyl-AMP by reaction with ATP and loss of diphosphate, and that the β-lactam ring is then formed by the intramolecular attack of the β-nitrogen on the activated carboxy group.
References:
1.  Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A. and Solomon, E.I. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: Correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123 (2001) 7388–7398. [PMID: 11472170]
2.  Townsend, C.A. New reactions in clavulanic acid biosynthesis. Curr. Opin. Chem. Biol. 6 (2002) 583–589. [PMID: 12413541]
3.  Bachmann, B.O., Li, R. and Townsend, C.A. β-Lactam synthetase: a new biosynthetic enzyme. Proc. Natl. Acad. Sci. USA 95 (1998) 9082–9086. [PMID: 9689037]
[EC 6.3.3.4 created 2003]
 
 
EC 6.3.3.5     
Accepted name: O-ureido-D-serine cyclo-ligase
Reaction: O-ureido-D-serine + ATP + H2O = D-cycloserine + CO2 + NH3 + ADP + phosphate
Glossary: O-ureido-D-serine = (2R)-2-amino-3-[(carbamoylamino)oxy]propanoate
Other name(s): dcsG (gene name)
Systematic name: O-ureido-D-serine cyclo-ligase (D-cycloserine-forming)
Comments: The enzyme participates in the biosynthetic pathway of D-cycloserine, an antibiotic substance produced by several Streptomyces species.
References:
1.  Kumagai, T., Koyama, Y., Oda, K., Noda, M., Matoba, Y. and Sugiyama, M. Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae. Antimicrob. Agents Chemother. 54 (2010) 1132–1139. [PMID: 20086163]
2.  Uda, N., Matoba, Y., Kumagai, T., Oda, K., Noda, M. and Sugiyama, M. Establishment of an in vitro D-cycloserine-synthesizing system by using O-ureido-L-serine synthase and D-cycloserine synthetase found in the biosynthetic pathway. Antimicrob. Agents Chemother. 57 (2013) 2603–2612. [PMID: 23529730]
[EC 6.3.3.5 created 2013]
 
 
EC 6.3.3.6     
Accepted name: carbapenam-3-carboxylate synthase
Reaction: ATP + (2S,5S)-5-carboxymethylproline = AMP + diphosphate + (3S,5S)-carbapenam 3-carboxylate
Other name(s): CarA (ambiguous); CPS (ambiguous); carbapenam-3-carboxylate ligase; 6-methyl-(2S,5S)-5-carboxymethylproline cyclo-ligase (AMP-forming)
Systematic name: (2S,5S)-5-carboxymethylproline cyclo-ligase (AMP-forming)
Comments: The enzyme is involved in the biosynthesis of the carbapenem β-lactam antibiotic (5R)-carbapen-2-em-3-carboxylate in the bacterium Pectobacterium carotovorum.
References:
1.  Gerratana, B., Stapon, A. and Townsend, C.A. Inhibition and alternate substrate studies on the mechanism of carbapenam synthetase from Erwinia carotovora. Biochemistry 42 (2003) 7836–7847. [PMID: 12820893]
2.  Miller, M.T., Gerratana, B., Stapon, A., Townsend, C.A. and Rosenzweig, A.C. Crystal structure of carbapenam synthetase (CarA). J. Biol. Chem. 278 (2003) 40996–41002. [PMID: 12890666]
3.  Raber, M.L., Arnett, S.O. and Townsend, C.A. A conserved tyrosyl-glutamyl catalytic dyad in evolutionarily linked enzymes: carbapenam synthetase and β-lactam synthetase. Biochemistry 48 (2009) 4959–4971. [PMID: 19371088]
4.  Arnett, S.O., Gerratana, B. and Townsend, C.A. Rate-limiting steps and role of active site Lys443 in the mechanism of carbapenam synthetase. Biochemistry 46 (2007) 9337–9345. [PMID: 17658887]
[EC 6.3.3.6 created 2013 as 6.3.1.16, transferred 2013 to EC 6.3.3.6]
 
 
EC 6.3.3.7     
Accepted name: Ni-sirohydrochlorin a,c-diamide reductive cyclase
Reaction: ATP + Ni-sirohydrochlorin a,c-diamide + 3 reduced electron acceptor + H2O = ADP + phosphate + 15,173-seco-F430-173-acid + 3 electron acceptor
Other name(s): cfbC (gene name); cfbD (gene name)
Systematic name: Ni-sirohydrochlorin a,c-diamide reductive cyclo-ligase (ADP-forming)
Comments: The enzyme, studied from the methanogenic archaeon Methanosarcina acetivorans, participates in the biosynthesis of the nickel-containing tetrapyrrole cofactor coenzyme F430, which is required by EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase.
References:
1.  Pfaltz, A., Kobelt, A., Huster, R. and Thauer, R.K. Biosynthesis of coenzyme F430 in methanogenic bacteria. Identification of 15,173-seco-F430-173-acid as an intermediate. Eur. J. Biochem. 170 (1987) 459–467. [PMID: 3691535]
2.  Zheng, K., Ngo, P.D., Owens, V.L., Yang, X.P. and Mansoorabadi, S.O. The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea. Science 354 (2016) 339–342. [PMID: 27846569]
[EC 6.3.3.7 created 2017]
 
 
EC 6.3.4.1      
Transferred entry: GMP synthase. Now included in EC 6.3.5.2, GMP synthase (glutamine-hydrolysing)
[EC 6.3.4.1 created 1961, deleted 2013]
 
 
EC 6.3.4.2     
Accepted name: CTP synthase (glutamine hydrolysing)
Reaction: ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + UTP + NH3 = ADP + phosphate + CTP
Other name(s): UTP—ammonia ligase; cytidine triphosphate synthetase; uridine triphosphate aminase; cytidine 5′-triphosphate synthetase; CTPS (gene name); pyrG (gene name); CTP synthase; UTP:ammonia ligase (ADP-forming)
Systematic name: UTP:L-glutamine amido-ligase (ADP-forming)
Comments: The enzyme contains three functionally distinct sites: an allosteric GTP-binding site, a glutaminase site where glutamine hydrolysis occurs (cf. EC 3.5.1.2, glutaminase), and the active site where CTP synthesis takes place. The reaction proceeds via phosphorylation of UTP by ATP to give an activated intermediate 4-phosphoryl UTP and ADP [4,5]. Ammonia then reacts with this intermediate generating CTP and a phosphate. The enzyme can also use ammonia from the surrounding solution [3,6].
References:
1.  Lieberman, I. Enzymatic amination of uridine triphosphate to cytidine triphosphate. J. Biol. Chem. 222 (1956) 765–775. [PMID: 13367044]
2.  Long, C.W., Levitzki, A., Houston, L.L and Koshland, D.E., Jr. Subunit structures and interactions of CTP synthetase. Fed. Proc. 28 (1969) 342.
3.  Levitzki, A. and Koshland, D.E., Jr. Ligand-induced dimer-to-tetramer transformation in cytosine triphosphate synthetase. Biochemistry 11 (1972) 247–253. [PMID: 4550560]
4.  von der Saal, W., Anderson, P.M. and Villafranca, J.J. Mechanistic investigations of Escherichia coli cytidine-5′-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments. J. Biol. Chem. 260 (1985) 14993–14997. [PMID: 2933396]
5.  Lewis, D.A. and Villafranca, J.J. Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods. Biochemistry 28 (1989) 8454–8459. [PMID: 2532543]
6.  Wadskov-Hansen, S.L., Willemoes, M., Martinussen, J., Hammer, K., Neuhard, J. and Larsen, S. Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase. J. Biol. Chem. 276 (2001) 38002–38009. [PMID: 11500486]
[EC 6.3.4.2 created 1961, modified 2013]
 
 
EC 6.3.4.3     
Accepted name: formate—tetrahydrofolate ligase
Reaction: ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate
Other name(s): formyltetrahydrofolate synthetase; 10-formyltetrahydrofolate synthetase; tetrahydrofolic formylase; tetrahydrofolate formylase
Systematic name: formate:tetrahydrofolate ligase (ADP-forming)
Comments: In eukaryotes occurs as a trifunctional enzyme also having methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activity.
References:
1.  Jaenicke, L. and Brode, E. Untersuchungen über Einkohlenstoffkörper. I. Die Tetrahydrofolatformylase aus Taubenleber. Rinigung und Mechanismus. Biochem. Z. 334 (1961) 108–132. [PMID: 13789141]
2.  Long, C.W., Levitzki, A., Houston, L.L and Koshland, D.E., Jr. Subunit structures and interactions of CTP synthetase. Fed. Proc. 28 (1969) 342.
3.  Rabinowitz, J.C. and Pricer, W.E. Formyltetrahydrofolate synthetase. I. Isolation and crystallization of the enzyme. J. Biol. Chem. 237 (1962) 2898–2902. [PMID: 14489619]
4.  Whiteley, H.R., Osborn, M.J. and Huennekens, F.M. Purification and properties of the formate-activating enzyme from Micrococcus aerogenes. J. Biol. Chem. 234 (1959) 1538–1543. [PMID: 13654413]
[EC 6.3.4.3 created 1961]
 
 
EC 6.3.4.4     
Accepted name: adenylosuccinate synthase
Reaction: GTP + IMP + L-aspartate = GDP + phosphate + N6-(1,2-dicarboxyethyl)-AMP
Other name(s): IMP—aspartate ligase; adenylosuccinate synthetase; succinoadenylic kinosynthetase; succino-AMP synthetase
Systematic name: IMP:L-aspartate ligase (GDP-forming)
References:
1.  Davey, C.L. Synthesis of adenylosuccinic acid in preparations of mammalian skeletal muscle. Nature 183 (1959) 995–996. [PMID: 13644270]
2.  Lieberman, I. Enzymatic synthesis of adenosine-5′-phosphate from inosine-5′-phosphate. J. Biol. Chem. 223 (1956) 327–339. [PMID: 13376602]
3.  Yefimochkina, E.F. and Braunstein, A.E. The amination of inosinic acid to adenylic acid in muscle extracts. Arch. Biochem. Biophys. 83 (1959) 350–352. [PMID: 13662023]
[EC 6.3.4.4 created 1961]
 
 
EC 6.3.4.5     
Accepted name: argininosuccinate synthase
Reaction: ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nω-L-arginino)succinate
Other name(s): citrulline—aspartate ligase; argininosuccinate synthetase; arginine succinate synthetase; argininosuccinic acid synthetase; arginosuccinate synthetase
Systematic name: L-citrulline:L-aspartate ligase (AMP-forming)
References:
1.  Ratner, S. Urea synthesis and metabolism of arginine and citrulline. Adv. Enzymol. Relat. Subj. Biochem. 15 (1954) 319–387. [PMID: 13158183]
2.  Schuegraf, A., Ratner, S. and Warner, R.C. Free energy changes of the argininosuccinate synthetase reaction and of the hydrolysis of the inner pyrophosphate bond of adenosine triphosphate. J. Biol. Chem. 235 (1960) 3597–3602. [PMID: 13748745]
[EC 6.3.4.5 created 1961]
 
 
EC 6.3.4.6     
Accepted name: urea carboxylase
Reaction: ATP + urea + HCO3- = ADP + phosphate + urea-1-carboxylate
Glossary: urea-1-carboxylate = allophanate
Other name(s): urease (ATP-hydrolysing); urea carboxylase (hydrolysing); ATP—urea amidolyase; urea amidolyase; UALase; UCA
Systematic name: urea:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein. The yeast enzyme (but not that from green algae) also catalyses the reaction of EC 3.5.1.54 allophanate hydrolase, thus bringing about the hydrolysis of urea to CO2 and NH3. Previously also listed as EC 3.5.1.45. The enzyme from the prokaryotic bacterium Oleomonas sagaranensis can also use acetamide and formamide as substrates [4].
References:
1.  Roon, R.J. and Levenberg, B. ATP-Urea amidolyase (ADP) (Candida utilis). Methods Enzymol. 17A (1970) 317–324.
2.  Roon, R.J. and Levenberg, B. Urea amidolyase. I. Properties of the enzyme from Candida utilis. J. Biol. Chem. 247 (1972) 4107–4113. [PMID: 4556303]
3.  Sumrada, R.A. and Cooper, T.G. Urea carboxylase and allophanate hydrolase are components of a multifunctional protein in yeast. J. Biol. Chem. 257 (1982) 9119–9127. [PMID: 6124544]
4.  Kanamori, T., Kanou, N., Atomi, H. and Imanaka, T. Enzymatic characterization of a prokaryotic urea carboxylase. J. Bacteriol. 186 (2004) 2532–2539. [PMID: 15090492]
[EC 6.3.4.6 created 1972, modified 1986 (EC 3.5.1.45 created 1978, incorporated 1986)]
 
 
EC 6.3.4.7     
Accepted name: ribose-5-phosphate—ammonia ligase
Reaction: ATP + ribose 5-phosphate + NH3 = ADP + phosphate + 5-phosphoribosylamine
Other name(s): 5-phosphoribosylamine synthetase; ribose 5-phosphate aminotransferase; ammonia-ribose 5-phosphate aminotransferase
Systematic name: ribose-5-phosphate:ammonia ligase (ADP-forming)
References:
1.  Reem, G.H. Enzymatic synthesis of 5′-phosphoribosylamine from ribose 5-phosphate and ammonia, an alternate first step in purine biosynthesis. J. Biol. Chem. 243 (1968) 5695–5701. [PMID: 5699059]
[EC 6.3.4.7 created 1972]
 
 
EC 6.3.4.8     
Accepted name: imidazoleacetate—phosphoribosyldiphosphate ligase
Reaction: ATP + imidazole-4-acetate + 5-phosphoribosyl diphosphate = ADP + phosphate + 1-(5-phosphoribosyl)imidazole-4-acetate + diphosphate
Other name(s): 5-phosphoribosylimidazoleacetate synthetase
Systematic name: imidazoleacetate:5-phosphoribosyl-diphosphate ligase (ADP- and diphosphate-forming)
References:
1.  Crowley, G.M. The enzymatic synthesis of 5′-phosphoribosylimidazoleacetic acid. J. Biol. Chem. 239 (1964) 2593–2601. [PMID: 14235540]
[EC 6.3.4.8 created 1972]
 
 
EC 6.3.4.9     
Accepted name: biotin—[methylmalonyl-CoA-carboxytransferase] ligase
Reaction: ATP + biotin + apo-[methylmalonyl-CoA:pyruvate carboxytransferase] = AMP + diphosphate + [methylmalonyl-CoA:pyruvate carboxytransferase]
Other name(s): biotin-[methylmalonyl-CoA-carboxyltransferase] synthetase; biotin-methylmalonyl coenzyme A carboxyltransferase synthetase; biotin-transcarboxylase synthetase; methylmalonyl coenzyme A holotranscarboxylase synthetase; biotin—[methylmalonyl-CoA-carboxyltransferase] ligase; biotin:apo[methylmalonyl-CoA:pyruvate carboxyltransferase] ligase (AMP-forming)
Systematic name: biotin:apo[methylmalonyl-CoA:pyruvate carboxytransferase] ligase (AMP-forming)
References:
1.  Lane, M.D., Young, D.L. and Lynen, F. The enzymatic synthesis of holotranscarboxylase from apotranscarboxylase and (+)-biotin. I. Purification of the apoenzyme and synthetase; characteristics of the reaction. J. Biol. Chem. 239 (1964) 2858–2864. [PMID: 14216436]
[EC 6.3.4.9 created 1972]
 
 
EC 6.3.4.10     
Accepted name: biotin—[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase
Reaction: ATP + biotin + apo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [propionyl-CoA:carbon-dioxide ligase (ADP-forming)]
Other name(s): biotin-[propionyl-CoA-carboxylase (ATP-hydrolysing)] synthetase; biotin-propionyl coenzyme A carboxylase synthetase; propionyl coenzyme A holocarboxylase synthetase
Systematic name: biotin:apo-[propanoyl-CoA:carbon-dioxide ligase (ADP-forming)] ligase (AMP-forming)
References:
1.  Siegel, L., Foote, J.L. and Coon, M.J. The enzymatic synthesis of propionyl coenzyme A holocarboxylase from d-biotinyl 5′-adenylate and the apocarboxylase. J. Biol. Chem. 240 (1965) 1025–1031. [PMID: 14284697]
[EC 6.3.4.10 created 1972]
 
 
EC 6.3.4.11     
Accepted name: biotin—[methylcrotonoyl-CoA-carboxylase] ligase
Reaction: ATP + biotin + apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)]
Other name(s): biotin-[methylcrotonoyl-CoA-carboxylase] synthetase; biotin-β-methylcrotonyl coenzyme A carboxylase synthetase; β-methylcrotonyl coenzyme A holocarboxylase synthetase; holocarboxylase-synthetase
Systematic name: biotin:apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] ligase (AMP-forming)
References:
1.  Höpner, T. and Knappe, J. Einbau von Biotin in β-methylcrotonyl-CoA-carboxylase urch Holocarboxylase-synthetase. Biochem. Z. 342 (1965) 190–206. [PMID: 5867144]
[EC 6.3.4.11 created 1972]
 
 
EC 6.3.4.12     
Accepted name: glutamate—methylamine ligase
Reaction: ATP + L-glutamate + methylamine = ADP + phosphate + N5-methyl-L-glutamine
Other name(s): γ-glutamylmethylamide synthetase
Systematic name: L-glutamate:methylamine ligase (ADP-forming)
References:
1.  Kung, H.-F. and Wagner, C. γ-Glutamylmethylamide. A new intermediate in the metabolism of methylamine. J. Biol. Chem. 244 (1969) 4136–4140. [PMID: 5800436]
[EC 6.3.4.12 created 1972]
 
 
EC 6.3.4.13     
Accepted name: phosphoribosylamine—glycine ligase
Reaction: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N1-(5-phospho-D-ribosyl)glycinamide
Other name(s): phosphoribosylglycinamide synthetase; glycinamide ribonucleotide synthetase; phosphoribosylglycineamide synthetase; glycineamide ribonucleotide synthetase; 2-amino-N-ribosylacetamide 5′-phosphate kinosynthase; 5′-phosphoribosylglycinamide synthetase; GAR
Systematic name: 5-phospho-D-ribosylamine:glycine ligase (ADP-forming)
References:
1.  Goldthwait, D.A., Peabody, R.A. and Greenberg, G.R. On the mechanism of synthesis of glycinamide ribotide and its formyl derivative. J. Biol. Chem. 221 (1956) 569–577. [PMID: 13357451]
2.  Hartman, S.C. and Buchanan, J.M. Biosynthesis of the purines. XXII. 2-Amino-N-ribosylacetamide-5′-phosphate kinosynthase. J. Biol. Chem. 233 (1958) 456–461. [PMID: 13563520]
[EC 6.3.4.13 created 1961 as EC 6.3.1.3, transferred 1972 to EC 6.3.4.13, modified 2000]
 
 
EC 6.3.4.14     
Accepted name: biotin carboxylase
Reaction: ATP + [biotin carboxyl-carrier protein]-biotin-N6-L-lysine + hydrogencarbonate- = ADP + phosphate + [biotin carboxyl-carrier protein]-carboxybiotin-N6-L-lysine
Other name(s): accC (gene name); biotin-carboxyl-carrier-protein:carbon-dioxide ligase (ADP-forming)
Systematic name: [biotin carboxyl-carrier protein]-biotin-N6-L-lysine:hydrogencarbonate ligase (ADP-forming)
Comments: This enzyme, part of an acetyl-CoA carboxylase complex, acts on a biotin carboxyl-carrier protein (BCCP) that has been biotinylated by EC 6.3.4.15, biotin—[biotin carboxyl-carrier protein] ligase. In some organisms the enzyme is part of a multi-domain polypeptide that also includes the carrier protein (e.g. mycobacteria). Yet in other organisms (e.g. mammals) this activity is included in a single polypeptide that also catalyses the transfer of the carboxyl group from biotin to acetyl-CoA (see EC 6.4.1.2, acetyl-CoA carboxylase).
References:
1.  Dimroth, P., Guchhait, R.B., Stoll, E. and Lane, M.D. Enzymatic carboxylation of biotin: molecular and catalytic properties of a component enzyme of acetyl CoA carboxylase. Proc. Natl. Acad. Sci. USA 67 (1970) 1353–1360. [PMID: 4922289]
2.  Norman, E., De Smet, K.A., Stoker, N.G., Ratledge, C., Wheeler, P.R. and Dale, J.W. Lipid synthesis in mycobacteria: characterization of the biotin carboxyl carrier protein genes from Mycobacterium leprae and M. tuberculosis. J. Bacteriol. 176 (1994) 2525–2531. [PMID: 7909542]
3.  Janiyani, K., Bordelon, T., Waldrop, G.L. and Cronan, J.E., Jr. Function of Escherichia coli biotin carboxylase requires catalytic activity of both subunits of the homodimer. J. Biol. Chem. 276 (2001) 29864–29870. [PMID: 11390406]
4.  Chou, C.Y., Yu, L.P. and Tong, L. Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism. J. Biol. Chem. 284 (2009) 11690–11697. [PMID: 19213731]
5.  Broussard, T.C., Pakhomova, S., Neau, D.B., Bonnot, R. and Waldrop, G.L. Structural analysis of substrate, reaction intermediate, and product binding in Haemophilus influenzae biotin carboxylase. Biochemistry 54 (2015) 3860–3870. [PMID: 26020841]
[EC 6.3.4.14 created 1976, modified 2014, modified 2018]
 
 
EC 6.3.4.15     
Accepted name: biotin—[biotin carboxyl-carrier protein] ligase
Reaction: ATP + biotin + [biotin carboxyl-carrier protein]-L-lysine = AMP + diphosphate + [biotin carboxyl-carrier protein]-N6-biotinyl-L-lysine
Other name(s): birA (gene name); HLCS (gene name); HCS1 (gene name); biotin-[acetyl-CoA carboxylase] synthetase; biotin-[acetyl coenzyme A carboxylase] synthetase; acetyl coenzyme A holocarboxylase synthetase; acetyl CoA holocarboxylase synthetase; biotin:apocarboxylase ligase; Biotin holoenzyme synthetase; biotin:apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] ligase (AMP-forming); biotin—[acetyl-CoA-carboxylase] ligase
Systematic name: biotin:apo-[carboxyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme biotinylates a biotin carboxyl-carrier protein that is part of an acetyl-CoA carboxylase complex, enabling its subsequent carboxylation by EC 6.3.4.14, biotin carboxylase. The carboxyl group is eventually transferred to acetyl-CoA by EC 2.1.3.15, acetyl-CoA carboxytransferase. In some organisms the carrier protein is part of EC 6.4.1.2, acetyl-CoA carboxylase.
References:
1.  Landman, A.D. and Dakshinamurti, K. Acetyl-Coenzyme A carboxylase. Role of the prosthetic group in enzyme polymerization. Biochem. J. 145 (1975) 545–548. [PMID: 239688]
2.  Wilson, K.P., Shewchuk, L.M., Brennan, R.G., Otsuka, A.J. and Matthews, B.W. Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc. Natl. Acad. Sci. USA 89 (1992) 9257–9261. [PMID: 1409631]
3.  Nenortas, E. and Beckett, D. Purification and characterization of intact and truncated forms of the Escherichia coli biotin carboxyl carrier subunit of acetyl-CoA carboxylase. J. Biol. Chem. 271 (1996) 7559–7567. [PMID: 8631788]
[EC 6.3.4.15 created 1978, modified 2018]
 
 
EC 6.3.4.16     
Accepted name: carbamoyl-phosphate synthase (ammonia)
Reaction: 2 ATP + NH3 + hydrogencarbonate = 2 ADP + phosphate + carbamoyl phosphate (overall reaction)
(1a) ATP + hydrogencarbonate = ADP + carboxyphosphate
(1b) NH3 + carboxyphosphate = carbamate + phosphate
(1c) ATP + carbamate = ADP + carbamoyl phosphate
Other name(s): carbon-dioxide—ammonia ligase; carbamoylphosphate synthase; carbamylphosphate synthetase; carbamoylphosphate synthase (ammonia); carbamoylphosphate synthetase; carbamylphosphate synthetase I; CPSI (gene name); carbon-dioxide:ammonia ligase (ADP-forming, carbamate-phosphorylating)
Systematic name: hydrogencarbonate:ammonia ligase (ADP-forming, carbamate-phosphorylating)
Comments: The enzyme catalyses the first committed step in the urea cycle. The reaction proceeds via three separate chemical reactions: phosphorylation of hydrogencarbonate to carboxyphosphate; a nucleophilic attack of ammonia on carboxyphosphate yielding carbamate; and the phosphorylation of carbamate forming carbamoyl phosphate. Two moles of ATP are utilized for the synthesis of one molecule of carbamyl phosphate, making the reaction essentially irreversible. The enzyme requires the allosteric activator N-acetyl-L-glutamate. cf. EC 6.3.5.5, carbamoyl-phosphate synthase (glutamine-hydrolysing).
References:
1.  Fahien, L.A. and Cohen, P.P. A kinetic study of carbamyl phosphate synthetase. J. Biol. Chem. 239 (1964) 1925–1934. [PMID: 14213379]
2.  Jones, M.E. and Spector, L. The pathway of carbonate in the biosynthesis of carbamyl phosphate. J. Biol. Chem. 235 (1960) 2897–2901. [PMID: 13790558]
3.  Marshall, M., Metzenberg, R.L. and Cohen, P.P. Purification of carbamyl phosphate synthetase from frog liver. J. Biol. Chem. 233 (1958) 102–105. [PMID: 13563449]
4.  Marshall, M., Metzenberg, R.L. and Cohen, P.P. Physical and kinetic properties of carbamyl phosphate synthetase from frog liver. J. Biol. Chem. 236 (1961) 2229–2237. [PMID: 26151989]
5.  Pierson, D.L. and Brien, J.M. Human carbamylphosphate synthetase I. Stabilization, purification, and partial characterization of the enzyme from human liver. J. Biol. Chem. 255 (1980) 7891–7895. [PMID: 6249820]
6.  Pekkala, S., Martinez, A.I., Barcelona, B., Gallego, J., Bendala, E., Yefimenko, I., Rubio, V. and Cervera, J. Structural insight on the control of urea synthesis: identification of the binding site for N-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase. Biochem. J. 424 (2009) 211–220. [PMID: 19754428]
[EC 6.3.4.16 created 1965 as EC 2.7.2.5, transferred 1978 to EC 6.3.4.16]
 
 
EC 6.3.4.17     
Accepted name: formate—dihydrofolate ligase
Reaction: ATP + formate + dihydrofolate = ADP + phosphate + 10-formyldihydrofolate
Other name(s): formyltransferase, dihydrofolate; dihydrofolate formyltransferase; formyl dihydrofolate synthase
Systematic name: formate:dihydrofolate ligase (ADP-forming)
Comments: Not identical with EC 6.3.4.3 (formate—tetrahydrofolate ligase).
References:
1.  Drake, J.C., Baram, J. and Allegra, C.J. Isolation and characterization of a novel dihydrofolate formylating enzyme from human MCF-7 breast cancer cells. Biochem. Pharmacol. 39 (1990) 615–618. [PMID: 2306274]
[EC 6.3.4.17 created 1992]
 
 
EC 6.3.4.18     
Accepted name: 5-(carboxyamino)imidazole ribonucleotide synthase
Reaction: ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole + HCO3- = ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole
Other name(s): N5-CAIR synthetase; N5-carboxyaminoimidazole ribonucleotide synthetase; PurK
Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole:carbon-dioxide ligase (ADP-forming)
Comments: In Escherichia coli, this enzyme, along with EC 5.4.99.18, 5-(carboxyamino)imidazole ribonucleotide mutase, is required to carry out the single reaction catalysed by EC 4.1.1.21, phosphoribosylaminoimidazole carboxylase, in vertebrates. Belongs to the ATP grasp protein superfamily [3]. Carboxyphosphate is the putative acyl phosphate intermediate. Involved in the late stages of purine biosynthesis.
References:
1.  Meyer, E., Leonard, N.J., Bhat, B., Stubbe, J. and Smith, J.M. Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway. Biochemistry 31 (1992) 5022–5032. [PMID: 1534690]
2.  Mueller, E.J., Meyer, E., Rudolph, J., Davisson, V.J. and Stubbe, J. N5-Carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli. Biochemistry 33 (1994) 2269–2278. [PMID: 8117684]
3.  Thoden, J.B., Kappock, T.J., Stubbe, J. and Holden, H.M. Three-dimensional structure of N5-carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein superfamily. Biochemistry 38 (1999) 15480–15492. [PMID: 10569930]
[EC 6.3.4.18 created 2006]
 
 
EC 6.3.4.19     
Accepted name: tRNAIle-lysidine synthase
Reaction: [tRNAIle2]-cytidine34 + L-lysine + ATP = [tRNAIle2]-lysidine34 + AMP + diphosphate + H2O
Glossary: lysidine = N6-(4-amino-1-β-D-ribofuranosylpyrimidin-2-ylidene)-L-lysine
Other name(s): TilS; mesJ (gene name); yacA (gene name); isoleucine-specific transfer ribonucleate lysidine synthetase; tRNAIle-lysidine synthetase
Systematic name: L-lysine:[tRNAIle2]-cytidine34 ligase (AMP-forming)
Comments: The bacterial enzyme modifies the wobble base of the CAU anticodon of tRNAIle at the oxo group in position 2 of cytidine34. This modification determines both codon and amino acid specificities of tRNAIle.
References:
1.  Ikeuchi, Y., Soma, A., Ote, T., Kato, J., Sekine, Y. and Suzuki, T. molecular mechanism of lysidine synthesis that determines tRNA identity and codon recognition. Mol. Cell 19 (2005) 235–246. [PMID: 16039592]
2.  Salowe, S.P., Wiltsie, J., Hawkins, J.C. and Sonatore, L.M. The catalytic flexibility of tRNAIle-lysidine synthetase can generate alternative tRNA substrates for isoleucyl-tRNA synthetase. J. Biol. Chem. 284 (2009) 9656–9662. [PMID: 19233850]
3.  Nakanishi, K., Fukai, S., Ikeuchi, Y., Soma, A., Sekine, Y., Suzuki, T. and Nureki, O. Structural basis for lysidine formation by ATP pyrophosphatase accompanied by a lysine-specific loop and a tRNA-recognition domain. Proc. Natl. Acad. Sci. USA 102 (2005) 7487–7492. [PMID: 15894617]
4.  Soma, A., Ikeuchi, Y., Kanemasa, S., Kobayashi, K., Ogasawara, N., Ote, T., Kato, J., Watanabe, K., Sekine, Y. and Suzuki, T. An RNA-modifying enzyme that governs both the codon and amino acid specificities of isoleucine tRNA. Mol. Cell 12 (2003) 689–698. [PMID: 14527414]
5.  Nakanishi, K., Bonnefond, L., Kimura, S., Suzuki, T., Ishitani, R. and Nureki, O. Structural basis for translational fidelity ensured by transfer RNA lysidine synthetase. Nature 461 (2009) 1144–1148. [PMID: 19847269]
[EC 6.3.4.19 created 2011]
 
 
EC 6.3.4.20     
Accepted name: 7-cyano-7-deazaguanine synthase
Reaction: 7-carboxy-7-carbaguanine + NH3 + ATP = 7-cyano-7-carbaguanine + ADP + phosphate + H2O
Glossary: preQ0 = 7-cyano-7-carbaguanine = 7-cyano-7-deazaguanine
7-carboxy-7-carbaguanine = 7-carboxy-7-deazaguanine
Other name(s): preQ0 synthase; 7-cyano-7-carbaguanine synthase; queC (gene name)
Systematic name: 7-carboxy-7-carbaguanine:ammonia ligase (ADP-forming)
Comments: Binds Zn2+. The reaction is part of the biosynthesis pathway of queuosine.
References:
1.  McCarty, R.M., Somogyi, A., Lin, G., Jacobsen, N.E. and Bandarian, V. The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of preQ0 from guanosine 5′-triphosphate in four steps. Biochemistry 48 (2009) 3847–3852. [PMID: 19354300]
2.  Cicmil, N. and Huang, R.H. Crystal structure of QueC from Bacillus subtilis: an enzyme involved in preQ1 biosynthesis. Proteins 72 (2008) 1084–1088. [PMID: 18491386]
[EC 6.3.4.20 created 2012]
 
 
EC 6.3.4.21     
Accepted name: nicotinate phosphoribosyltransferase
Reaction: nicotinate + 5-phospho-α-D-ribose 1-diphosphate + ATP + H2O = β-nicotinate D-ribonucleotide + diphosphate + ADP + phosphate
Other name(s): niacin ribonucleotidase; nicotinic acid mononucleotide glycohydrolase; nicotinic acid mononucleotide pyrophosphorylase; nicotinic acid phosphoribosyltransferase; nicotinate-nucleotide:diphosphate phospho-α-D-ribosyltransferase
Systematic name: 5-phospho-α-D-ribose 1-diphosphate:nicotinate ligase (ADP, diphosphate-forming)
Comments: The enzyme, which is involved in pyridine nucleotide recycling, can form β-nicotinate D-ribonucleotide and diphosphate from nicotinate and 5-phospho-α-D-ribose 1-diphosphate (PRPP) in the absence of ATP. However, when ATP is available the enzyme is phosphorylated resulting in a much lower Km for nicotinate. The phospho-enzyme is hydrolysed during the transferase reaction, regenerating the low affinity form. The presence of ATP shifts the products/substrates equilibrium from 0.67 to 1100 [4].
References:
1.  Imsande, J. Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli. J. Biol. Chem. 236 (1961) 1494–1497. [PMID: 13717628]
2.  Imsande, J. and Handler, P. Biosynthesis of diphosphopyridine nucleotide. III. Nicotinic acid mononucleotide pyrophosphorylase. J. Biol. Chem. 236 (1961) 525–530. [PMID: 13717627]
3.  Kosaka, A., Spivey, H.O. and Gholson, R.K. Nicotinate phosphoribosyltransferase of yeast. Purification and properties. J. Biol. Chem. 246 (1971) 3277–3283. [PMID: 4324895]
4.  Vinitsky, A. and Grubmeyer, C. A new paradigm for biochemical energy coupling. Salmonella typhimurium nicotinate phosphoribosyltransferase. J. Biol. Chem. 268 (1993) 26004–26010. [PMID: 7503993]
[EC 6.3.4.21 created 1961 as EC 2.4.2.11, transferred 2013 to EC 6.3.4.21]
 
 
EC 6.3.4.22     
Accepted name: tRNAIle2-agmatinylcytidine synthase
Reaction: ATP + agmatine + [tRNAIle2]-cytidine34 + H2O = [tRNAIle2]-2-agmatinylcytidine34 + AMP + 2 phosphate
Other name(s): TiaS; AF2259; tRNAIle-2-agmatinylcytidine synthetase; tRNAIle-agm2C synthetase; tRNAIle-agmatidine synthetase
Systematic name: agmatine:[tRNAIle]-cytidine34 ligase
Comments: The enzyme from the archaeon Archaeoglobus fulgidus modifies the wobble base of the CAU anticodon of the archaeal tRNAIle2 at the oxo group in position 2 of cytidine34. This modification is crucial for accurate decoding of the genetic code. In bacteria EC 6.3.4.19, tRNAIle-lysidine synthase, catalyses the modification of [tRNAIle2]-cytidine34 to [tRNAIle2]-lysidine34 .
References:
1.  Ikeuchi, Y., Kimura, S., Numata, T., Nakamura, D., Yokogawa, T., Ogata, T., Wada, T., Suzuki, T. and Suzuki, T. Agmatine-conjugated cytidine in a tRNA anticodon is essential for AUA decoding in archaea. Nat. Chem. Biol. 6 (2010) 277–282. [PMID: 20139989]
2.  Terasaka, N., Kimura, S., Osawa, T., Numata, T. and Suzuki, T. Biogenesis of 2-agmatinylcytidine catalyzed by the dual protein and RNA kinase TiaS. Nat. Struct. Mol. Biol. 18 (2011) 1268–1274. [PMID: 22002222]
3.  Osawa, T., Inanaga, H., Kimura, S., Terasaka, N., Suzuki, T. and Numata, T. Crystallization and preliminary X-ray diffraction analysis of an archaeal tRNA-modification enzyme, TiaS, complexed with tRNA(Ile2) and ATP. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67 (2011) 1414–1416. [PMID: 22102245]
[EC 6.3.4.22 created 2013]
 
 
EC 6.3.4.23     
Accepted name: formate—phosphoribosylaminoimidazolecarboxamide ligase
Reaction: ATP + formate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = ADP + phosphate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
Other name(s): 5-formaminoimidazole-4-carboxamide ribonucleotide synthetase; 5-formaminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate synthetase; purP (gene name)
Systematic name: formate:5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide ligase (ADP-forming)
Comments: This archaeal enzyme, characterized from the methanogen Methanocaldococcus jannaschii, catalyses a step in the synthesis of purine nucleotides. It differs from the orthologous bacterial/eukaryotic enzymes, which utilize 10-formyltetrahydrofolate rather than formate and ATP. cf. EC 2.1.2.3, phosphoribosylaminoimidazolecarboxamide formyltransferase.
References:
1.  Ownby, K., Xu, H. and White, R.H. A Methanocaldococcus jannaschii archaeal signature gene encodes for a 5-formaminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate synthetase. A new enzyme in purine biosynthesis. J. Biol. Chem. 280 (2005) 10881–10887. [PMID: 15623504]
2.  Zhang, Y., White, R.H. and Ealick, S.E. Crystal structure and function of 5-formaminoimidazole-4-carboxamide ribonucleotide synthetase from Methanocaldococcus jannaschii. Biochemistry 47 (2008) 205–217. [PMID: 18069798]
[EC 6.3.4.23 created 2013]
 
 
EC 6.3.4.24     
Accepted name: tyramine—L-glutamate ligase
Reaction: ATP + tyramine + L-glutamate = ADP + phosphate + γ-glutamyltyramine
Other name(s): mfnD (gene name)
Systematic name: tyramine:L-glutamate γ-ligase (ADP-forming)
Comments: The enzyme, which has been characterized from the archaea Methanocaldococcus fervens, participates in the biosynthesis of the cofactor methanofuran. Requires a divalent cation for activity, with Mn2+ giving the highest activity, followed by Mg2+, Co2+, Zn2+, and Fe2+.
References:
1.  Wang, Y., Xu, H., Harich, K.C. and White, R.H. Identification and characterization of a tyramine-glutamate ligase (MfnD) Involved in methanofuran biosynthesis. Biochemistry 53 (2014) 6220–6230. [PMID: 25211225]
[EC 6.3.4.24 created 2014]
 
 
EC 6.3.5.1     
Accepted name: NAD+ synthase (glutamine-hydrolysing)
Reaction: ATP + deamido-NAD+ + L-glutamine + H2O = AMP + diphosphate + NAD+ + L-glutamate
Other name(s): NAD synthetase (glutamine-hydrolysing); nicotinamide adenine dinucleotide synthetase (glutamine); desamidonicotinamide adenine dinucleotide amidotransferase; DPN synthetase
Systematic name: deamido-NAD+:L-glutamine amido-ligase (AMP-forming)
Comments: NH3 can act instead of glutamine (cf. EC 6.3.1.5 NAD+ synthase).
References:
1.  Imsande, J. Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli. J. Biol. Chem. 236 (1961) 1494–1497. [PMID: 13717628]
2.  Imsande, J. and Handler, P. Biosynthesis of diphosphopyridine nucleotide. III. Nicotinic acid mononucleotide pyrophosphorylase. J. Biol. Chem. 236 (1961) 525–530. [PMID: 13717627]
[EC 6.3.5.1 created 1961]
 
 
EC 6.3.5.2     
Accepted name: GMP synthase (glutamine-hydrolysing)
Reaction: ATP + XMP + L-glutamine + H2O = AMP + diphosphate + GMP + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + XMP + NH3 = AMP + diphosphate + GMP
Glossary: XMP = xanthosine 5′-phosphate
Other name(s): GMP synthetase (glutamine-hydrolysing); guanylate synthetase (glutamine-hydrolyzing); guanosine monophosphate synthetase (glutamine-hydrolyzing); xanthosine 5′-phosphate amidotransferase; guanosine 5′-monophosphate synthetase
Systematic name: xanthosine-5′-phosphate:L-glutamine amido-ligase (AMP-forming)
Comments: Involved in the de novo biosynthesis of guanosine nucleotides. An N-terminal glutaminase domain binds L-glutamine and generates ammonia, which is transferred by a substrate-protective tunnel to the ATP-pyrophosphatase domain. The enzyme can catalyse the second reaction alone in the presence of ammonia.
References:
1.  Lagerkvist, U. Biosynthesis of guanosine 5′-phosphate. II. Amination of xanthosine 5′-phosphate by purified enzyme from pigeon liver. J. Biol. Chem. 233 (1958) 143–149. [PMID: 13563458]
2.  Abrams, R. and Bentley, M. Biosynthesis of nucleic acid purines. III. Guanosine 5′-phosphate formation from xanthosine 5′-phosphate and L-glutamine. Arch. Biochem. Biophys. 79 (1959) 91–110.
3.  Zalkin, H., Argos, P., Narayana, S.V., Tiedeman, A.A. and Smith, J.M. Identification of a trpG-related glutamine amide transfer domain in Escherichia coli GMP synthetase. J. Biol. Chem. 260 (1985) 3350–3354. [PMID: 2982857]
4.  Abbott, J.L., Newell, J.M., Lightcap, C.M., Olanich, M.E., Loughlin, D.T., Weller, M.A., Lam, G., Pollack, S. and Patton, W.A. The effects of removing the GAT domain from E. coli GMP synthetase. Protein J. 25 (2006) 483–491. [PMID: 17103135]
[EC 6.3.5.2 created 1961, modified 2013]
 
 
EC 6.3.5.3     
Accepted name: phosphoribosylformylglycinamidine synthase
Reaction: ATP + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H2O = ADP + phosphate + 2-(formamido)-N1-(5-phospho-D-ribosyl)acetamidine + L-glutamate
Other name(s): phosphoribosylformylglycinamidine synthetase; formylglycinamide ribonucleotide amidotransferase; phosphoribosylformylglycineamidine synthetase; FGAM synthetase; FGAR amidotransferase; 5′-phosphoribosylformylglycinamide:L-glutamine amido-ligase (ADP-forming); 2-N-formyl-1-N-(5-phospho-D-ribosyl)glycinamide:L-glutamine amido-ligase (ADP-forming)
Systematic name: N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide:L-glutamine amido-ligase (ADP-forming)
References:
1.  Melnick, I. and Buchanan, J.M. Biosynthesis of the purines. I. Conversion of (α-N-formyl)glycinamide ribotide to (α-N-formyl)glycinamidine ribotide; purification and requirements of the enzyme system. J. Biol. Chem. 225 (1957) 157–162. [PMID: 13416226]
[EC 6.3.5.3 created 1961, modified 2000]
 
 
EC 6.3.5.4     
Accepted name: asparagine synthase (glutamine-hydrolysing)
Reaction: ATP + L-aspartate + L-glutamine + H2O = AMP + diphosphate + L-asparagine + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + L-aspartate + NH3 = AMP + diphosphate + L-asparagine
Other name(s): asparagine synthetase (glutamine-hydrolysing); glutamine-dependent asparagine synthetase; asparagine synthetase B; AS; AS-B
Systematic name: L-aspartate:L-glutamine amido-ligase (AMP-forming)
Comments: The enzyme from Escherichia coli has two active sites [4] that are connected by an intramolecular ammonia tunnel [5,6]. The enzyme catalyses three distinct chemical reactions: glutamine hydrolysis to yield ammonia takes place in the N-terminal domain. The C-terminal active site mediates both the synthesis of a β-aspartyl-AMP intermediate and its subsequent reaction with ammonia. The ammonia released is channeled to the other active site to yield asparagine [6].
References:
1.  Patterson, M.K., Jr. and Orr, G.R. Asparagine biosynthesis by the Novikoff hepatoma. Isolation, purification, property, and mechanism studies of the enzyme system. J. Biol. Chem. 243 (1968) 376–380. [PMID: 4295091]
2.  Boehlein, S.K., Richards, N.G. and Schuster, S.M. Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad. J. Biol. Chem. 269 (1994) 7450–7457. [PMID: 7907328]
3.  Richards, N.G. and Schuster, S.M. Mechanistic issues in asparagine synthetase catalysis. Adv. Enzymol. Relat. Areas Mol. Biol. 72 (1998) 145–198. [PMID: 9559053]
4.  Larsen, T.M., Boehlein, S.K., Schuster, S.M., Richards, N.G., Thoden, J.B., Holden, H.M. and Rayment, I. Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product. Biochemistry 38 (1999) 16146–16157. [PMID: 10587437]
5.  Huang, X., Holden, H.M. and Raushel, F.M. Channeling of substrates and intermediates in enzyme-catalyzed reactions. Annu. Rev. Biochem. 70 (2001) 149–180. [PMID: 11395405]
6.  Tesson, A.R., Soper, T.S., Ciustea, M. and Richards, N.G. Revisiting the steady state kinetic mechanism of glutamine-dependent asparagine synthetase from Escherichia coli. Arch. Biochem. Biophys. 413 (2003) 23–31. [PMID: 12706338]
[EC 6.3.5.4 created 1972, modified 2006]
 
 
EC 6.3.5.5     
Accepted name: carbamoyl-phosphate synthase (glutamine-hydrolysing)
Reaction: 2 ATP + L-glutamine + hydrogencarbonate + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + hydrogencarbonate = ADP + carboxyphosphate
(1c) NH3 + carboxyphosphate = carbamate + phosphate
(1d) ATP + carbamate = ADP + carbamoyl phosphate
Other name(s): carbamoyl-phosphate synthetase (glutamine-hydrolysing); carbamyl phosphate synthetase (glutamine); carbamoylphosphate synthetase II; glutamine-dependent carbamyl phosphate synthetase; carbamoyl phosphate synthetase; CPS; carbon-dioxide:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating); carA (gene name); carB (gene name); CAD (gene name); hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
Systematic name: hydrogencarbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
Comments: The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 Å in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxyphosphate to produce the carbamate intermediate. The carboxyphosphate intermediate is formed by the phosphorylation of hydrogencarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6]. cf. EC 6.3.4.16, carbamoyl-phosphate synthase (ammonia).
References:
1.  Anderson, P.M. and Meister, A. Evidence for an activated form of carbon dioxide in the reaction catalysed by Escherichia coli carbamyl phosphate synthetase. Biochemistry 4 (1965) 2803–2809. [PMID: 5326356]
2.  Kalman, S.M., Duffield, P.H. and Brzozowski, T. Purification and properties of a bacterial carbamyl phosphate synthetase. J. Biol. Chem. 241 (1966) 1871–1877. [PMID: 5329589]
3.  Yip, M.C.M. and Knox, W.E. Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues. J. Biol. Chem. 245 (1970) 2199–2204. [PMID: 5442268]
4.  Stapleton, M.A., Javid-Majd, F., Harmon, M.F., Hanks, B.A., Grahmann, J.L., Mullins, L.S. and Raushel, F.M. Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. Biochemistry 35 (1996) 14352–14361. [PMID: 8916922]
5.  Holden, H.M., Thoden, J.B. and Raushel, F.M. Carbamoyl phosphate synthetase: a tunnel runs through it. Curr. Opin. Struct. Biol. 8 (1998) 679–685. [PMID: 9914247]
6.  Raushel, F.M., Thoden, J.B., Reinhart, G.D. and Holden, H.M. Carbamoyl phosphate synthetase: a crooked path from substrates to products. Curr. Opin. Chem. Biol. 2 (1998) 624–632. [PMID: 9818189]
7.  Raushel, F.M., Thoden, J.B. and Holden, H.M. The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Biochemistry 38 (1999) 7891–7899. [PMID: 10387030]
8.  Thoden, J.B., Huang, X., Raushel, F.M. and Holden, H.M. Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia. J. Biol. Chem. 277 (2002) 39722–39727. [PMID: 12130656]
[EC 6.3.5.5 created 1972 as EC 2.7.2.9, transferred 1978 to EC 6.3.5.5, modified 2006]
 
 
EC 6.3.5.6     
Accepted name: asparaginyl-tRNA synthase (glutamine-hydrolysing)
Reaction: ATP + L-aspartyl-tRNAAsn + L-glutamine + H2O = ADP + phosphate + L-asparaginyl-tRNAAsn + L-glutamate
Other name(s): Asp-AdT; Asp-tRNAAsn amidotransferase; aspartyl-tRNAAsn amidotransferase; Asn-tRNAAsn:L-glutamine amido-ligase (ADP-forming); aspartyl-tRNAAsn:L-glutamine amido-ligase (ADP-forming)
Systematic name: L-aspartyl-tRNAAsn:L-glutamine amido-ligase (ADP-forming)
Comments: This reaction forms part of a two-reaction system for producing asparaginyl-tRNA in Deinococcus radiodurans and other organisms lacking a specific enzyme for asparagine synthesis. In the first step, a non-discriminating ligase (EC 6.1.1.23, aspartate—tRNAAsn ligase) mischarges tRNAAsn with aspartate, leading to the formation of Asp-tRNAAsn. The aspartyl-tRNAAsn is not used in protein synthesis until the present enzyme converts it into asparaginyl-tRNAAsn (aspartyl-tRNAAsp is not a substrate for this reaction). Ammonia or asparagine can substitute for the preferred substrate glutamine.
References:
1.  Min, B., Pelaschier, J.T., Graham, D.E., Tumbula-Hansen, D. and Söll, D. Transfer RNA-dependent amino acid biosynthesis: an essential route to asparagine formation. Proc. Natl. Acad. Sci. USA 99 (2002) 2678–2683. [PMID: 11880622]
2.  Curnow, A.W., Tumbula, D.L., Pelaschier, J.T., Min, B. and Söll, D. Glutamyl-tRNAGln amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 12838–12843. [PMID: 9789001]
3.  Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617–650. [PMID: 10966471]
[EC 6.3.5.6 created 2002, modified 2012]
 
 
EC 6.3.5.7     
Accepted name: glutaminyl-tRNA synthase (glutamine-hydrolysing)
Reaction: ATP + L-glutamyl-tRNAGln + L-glutamine = ADP + phosphate + L-glutaminyl-tRNAGln + L-glutamate
Other name(s): Glu-AdT; Glu-tRNAGln amidotransferase; glutamyl-tRNAGln amidotransferase; Glu-tRNAGln:L-glutamine amido-ligase (ADP-forming)
Systematic name: L-glutamyl-tRNAGln:L-glutamine amido-ligase (ADP-forming)
Comments: In systems lacking discernible glutamine—tRNA ligase (EC 6.1.1.18), glutaminyl-tRNAGln is formed by a two-enzyme system. In the first step, a nondiscriminating ligase (EC 6.1.1.24, glutamate—tRNAGln ligase) mischarges tRNAGln with glutamate, forming glutamyl-tRNAGln. The glutamyl-tRNAGln is not used in protein synthesis until the present enzyme converts it into glutaminyl-tRNAGln (glutamyl-tRNAGlu is not a substrate for this reaction). Ammonia or asparagine can substitute for the preferred substrate glutamine.
References:
1.  Horiuchi, K.Y., Harpel, M.R., Shen, L., Luo, Y., Rogers, K.C. and Copeland, R.A. Mechanistic studies of reaction coupling in Glu-tRNAGln amidotransferase. Biochemistry 40 (2001) 6450–6457. [PMID: 11371208]
2.  Curnow, A.W., Tumbula, D.L., Pelaschier, J.T., Min, B. and Söll, D. Glutamyl-tRNAGln amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 12838–12843. [PMID: 9789001]
3.  Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617–650. [PMID: 10966471]
[EC 6.3.5.7 created 2002]
 
 
EC 6.3.5.8      
Transferred entry: aminodeoxychorismate synthase. Now EC 2.6.1.85, aminodeoxychorismate synthase. As ATP is not hydrolysed during the reaction, the classification of the enzyme as a ligase was incorrect
[EC 6.3.5.8 created 2003, deleted 2007]
 
 
EC 6.3.5.9     
Accepted name: hydrogenobyrinic acid a,c-diamide synthase (glutamine-hydrolysing)
Reaction: 2 ATP + hydrogenobyrinic acid + 2 L-glutamine + 2 H2O = 2 ADP + 2 phosphate + hydrogenobyrinic acid a,c-diamide + 2 L-glutamate
Other name(s): CobB
Systematic name: hydrogenobyrinic-acid:L-glutamine amido-ligase (AMP-forming)
Comments: This step in the aerobic biosynthesis of cobalamin generates hydrogenobyrinic acid a,c-diamide, the substrate required by EC 6.6.1.2, cobaltochelatase, which adds cobalt to the macrocycle.
References:
1.  Debussche, L., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Purification and characterization of cobyrinic acid a,c-diamide synthase from Pseudomonas denitrificans. J. Bacteriol. 172 (1990) 6239–6244. [PMID: 2172209]
2.  Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390–412. [PMID: 12195810]
[EC 6.3.5.9 created 2004]
 
 
EC 6.3.5.10     
Accepted name: adenosylcobyric acid synthase (glutamine-hydrolysing)
Reaction: 4 ATP + adenosylcobyrinic acid a,c-diamide + 4 L-glutamine + 4 H2O = 4 ADP + 4 phosphate + adenosylcobyric acid + 4 L-glutamate
Other name(s): CobQ; cobyric acid synthase; 5′-deoxy-5′-adenosylcobyrinic-acid-a,c-diamide:L-glutamine amido-ligase; Ado-cobyric acid synthase [glutamine hydrolyzing]
Systematic name: adenosylcobyrinic-acid-a,c-diamide:L-glutamine amido-ligase (ADP-forming)
Comments: Requires Mg2+. NH3 can act instead of glutamine. This enzyme catalyses the four-step amidation sequence from cobyrinic acid a,c-diamide to cobyric acid via the formation of cobyrinic acid triamide, tetraamide and pentaamide intermediates.
References:
1.  Blanche, F., Couder, M., Debussche, L., Thibaut, D., Cameron, B. and Crouzet, J. Biosynthesis of vitamin B12: stepwise amidation of carboxyl groups b, d, e, and g of cobyrinic acid a,c-diamide is catalyzed by one enzyme in Pseudomonas denitrificans. J. Bacteriol. 173 (1991) 6046–6051. [PMID: 1917839]
2.  Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390–412. [PMID: 12195810]
[EC 6.3.5.10 created 2004]
 
 
EC 6.3.5.11     
Accepted name: cobyrinate a,c-diamide synthase
Reaction: 2 ATP + cobyrinate + 2 L-glutamine + 2 H2O = 2 ADP + 2 phosphate + cobyrinate a,c-diamide + 2 L-glutamate (overall reaction)
(1a) ATP + cobyrinate + L-glutamine + H2O = ADP + phosphate + cobyrinate c-monamide + L-glutamate
(1b) ATP + cobyrinate c-monamide + L-glutamine + H2O = ADP + phosphate + cobyrinate a,c-diamide + L-glutamate
Other name(s): cobyrinic acid a,c-diamide synthetase; CbiA
Systematic name: cobyrinate:L-glutamine amido-ligase (ADP-forming)
Comments: This enzyme is the first glutamine amidotransferase that participates in the anaerobic (early cobalt insertion) biosynthetic pathway of adenosylcobalamin, and catalyses the ATP-dependent synthesis of cobyrinate a,c-diamide from cobyrinate using either L-glutamine or ammonia as the nitrogen source. It is proposed that the enzyme first catalyses the amidation of the c-carboxylate, and then the intermediate is released into solution and binds to the same catalytic site for the amidation of the a-carboxylate. The Km for ammonia is substantially higher than that for L-glutamine.
References:
1.  Fresquet, V., Williams, L. and Raushel, F.M. Mechanism of cobyrinic acid a,c-diamide synthetase from Salmonella typhimurium LT2. Biochemistry 43 (2004) 10619–10627. [PMID: 15311923]
[EC 6.3.5.11 created 2010]
 
 
EC 6.3.5.12     
Accepted name: Ni-sirohydrochlorin a,c-diamide synthase
Reaction: 2 ATP + Ni-sirohydrochlorin + 2 L-glutamine + 2 H2O = 2 ADP + 2 phosphate + Ni-sirohydrochlorin a,c-diamide + 2 L-glutamate
Other name(s): cfbB (gene name)
Systematic name: Ni-sirohydrochlorin:L-glutamine amido-ligase (ADP-forming)
Comments: The enzyme, studied from the methanogenic archaeon Methanosarcina acetivorans, participates in the biosynthesis of the nickel-containing tetrapyrrole cofactor coenzyme F430, which is required by EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase.
References:
1.  Zheng, K., Ngo, P.D., Owens, V.L., Yang, X.P. and Mansoorabadi, S.O. The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea. Science 354 (2016) 339–342. [PMID: 27846569]
[EC 6.3.5.12 created 2017]
 
 
EC 6.4.1.1     
Accepted name: pyruvate carboxylase
Reaction: ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
Other name(s): pyruvic carboxylase
Systematic name: pyruvate:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
References:
1.  McClure, W.R., Lardy, H.A. and Kneifel, H.P. Rat liver pyruvate carboxylase. I. Preparation, properties, and cation specificity. J. Biol. Chem. 246 (1971) 3569–3578. [PMID: 5578910]
2.  Scrutton, M.C., Young, M.R. and Utter, M.F. Pyruvate carboxylase from baker's yeast. The presence of bound zinc. J. Biol. Chem. 245 (1970) 6220–6227. [PMID: 5484476]
3.  Seubert, W. and Remberger, U. Renigung und Wirkungsweise der Pyruvatcarboxylase aus Pseudomonas citronellolis. Biochem. Z. 334 (1961) 401–414. [PMID: 13750403]
4.  Utter, M.F. and Keech, D.B. Pyruvate carboxylase. I. Nature of the reaction. J. Biol. Chem. 238 (1963) 2603–2608. [PMID: 14063279]
[EC 6.4.1.1 created 1961]
 
 
EC 6.4.1.2     
Accepted name: acetyl-CoA carboxylase
Reaction: ATP + acetyl-CoA + hydrogencarbonate = ADP + phosphate + malonyl-CoA
Other name(s): HFA1 (gene name); ACC1 (gene name); acetyl coenzyme A carboxylase; acetyl-CoA:carbon-dioxide ligase (ADP-forming)
Systematic name: acetyl-CoA:hydrogencarbonate ligase (ADP-forming)
Comments: This enzyme is a multi-domain polypeptide that catalyses three different activities - a biotin carboxyl-carrier protein (BCCP), a biotin carboxylase that catalyses the transfer of a carboxyl group from hydrogencarbonate to the biotin molecule carried by the carrier protein, and the transfer of the carboxyl group from biotin to acetyl-CoA, forming malonyl-CoA. In some organisms these activities are catalysed by separate enzymes (see EC 6.3.4.14, biotin carboxylase, and EC 2.1.3.15, acetyl-CoA carboxytransferase). The carboxylation of the carrier protein requires ATP, while the transfer of the carboxyl group to acetyl-CoA does not.
References:
1.  Wakil, S.J. A malonic acid derivative as an intermediate in fatty acid synthesis. J. Am. Chem. Soc. 80 (1958) 6465.
2.  Hatch, M.D. and Stumpf, P.K. Fat metabolism in higher plants. XVI. Acetyl coenzyme A carboxylase and acyl coenzyme A-malonyl coenzyme A transcarboxylase from wheat germ. J. Biol. Chem. 236 (1961) 2879–2885. [PMID: 13905314]
3.  Matsuhashi, M., Matsuhashi, S., Numa, S. and Lynen, F. Zur Biosynthese der Fettsäuren. IV Acetyl CoA Carboxylase aus Hefe. Biochem. Z. 340 (1964) 243–262. [PMID: 14317957]
4.  Matsuhashi, M., Matsuhashi, S. and Lynen, F. Zur Biosynthese der Fettsäuren. V. Die Acetyl-CoA Carboxylase aus Rattenleber und ihre Aktivierung durch Citronsäure. Biochem. Z. 340 (1964) 263–289. [PMID: 14317958]
5.  Vagelos, P. Regulation of fatty acid biosynthesis. Curr. Top. Cell. Regul. 4 (1971) 119–166.
6.  Trumble, G.E., Smith, M.A. and Winder, W.W. Purification and characterization of rat skeletal muscle acetyl-CoA carboxylase. Eur. J. Biochem. 231 (1995) 192–198. [PMID: 7628470]
7.  Cheng, D., Chu, C.H., Chen, L., Feder, J.N., Mintier, G.A., Wu, Y., Cook, J.W., Harpel, M.R., Locke, G.A., An, Y. and Tamura, J.K. Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes. Protein Expr. Purif. 51 (2007) 11–21. [PMID: 16854592]
8.  Kim, K.W., Yamane, H., Zondlo, J., Busby, J. and Wang, M. Expression, purification, and characterization of human acetyl-CoA carboxylase 2. Protein Expr. Purif. 53 (2007) 16–23. [PMID: 17223360]
[EC 6.4.1.2 created 1961, modified 2018]
 
 
EC 6.4.1.3     
Accepted name: propionyl-CoA carboxylase
Reaction: ATP + propanoyl-CoA + HCO3- = ADP + phosphate + (S)-methylmalonyl-CoA
Other name(s): propionyl coenzyme A carboxylase
Systematic name: propanoyl-CoA:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein. Also carboxylates butanoyl-CoA and catalyses transcarboxylation.
References:
1.  Kaziro, Y., Ochoa, S., Warner, R.C. and Chen, J.-Y. Metabolism of propionic acid in animal tissues. VIII. Crystalline propionyl carboxylase. J. Biol. Chem. 236 (1961) 1917–1923. [PMID: 13752080]
2.  Lane, M.D., Halenz, D.R., Kosow, D.P. and Hegre, C.S. Further studies on mitochondrial propionyl carboxylase. J. Biol. Chem. 235 (1960) 3082–3086. [PMID: 13758723]
3.  Meyer, H., Nevaldine, B. and Meyer, F. Acyl-coenzyme A carboxylase of the free-living nematode Turbatrix aceti. 1. Its isolation and molecular characteristics. Biochemistry 17 (1978) 1822–1827. [PMID: 656363]
4.  Moss, J. and Lane, M.D. The biotin-dependent enzymes. Adv. Enzymol. Relat. Areas Mol. Biol. 35 (1971) 321–442. [PMID: 4150153]
5.  Vagelos, P. Regulation of fatty acid biosynthesis. Curr. Top. Cell. Regul. 4 (1971) 119–166.
[EC 6.4.1.3 created 1961, modified 1983]
 
 
EC 6.4.1.4     
Accepted name: methylcrotonoyl-CoA carboxylase
Reaction: ATP + 3-methylcrotonoyl-CoA + HCO3- = ADP + phosphate + 3-methylglutaconyl-CoA
Other name(s): methylcrotonyl coenzyme A carboxylase; β-methylcrotonyl coenzyme A carboxylase; β-methylcrotonyl CoA carboxylase; methylcrotonyl-CoA carboxylase
Systematic name: 3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein.
References:
1.  Knappe, J., Schlegel, H.-G. and Lynen, F. Zur biochemischen Funktion des Biotins. I. Die Beteilligung der β-Methyl-crotonyl-Carboxylase an der Bildung von β-Hydroxy-β-methyl-glutaryl-CoA from β-Hydroxy-isovaleryl-CoA. Biochem. Z. 335 (1961) 101–122. [PMID: 14457200]
2.  Lynen, F., Knappe, J., Lorch, E., Jütting, G., Ringelmann, E. and Lachance, J.-P. Zur biochemischen Funktion des Biotins. II. Reinigung und Wirkungsweise der β-Methyl-crotonyl-Carboxlase. Biochem. Z. 335 (1961) 123–166. [PMID: 14467590]
3.  Rilling, H.C. and Coon, M.J. The enzymatic isomerization of α-methylvinylacetyl coenzyme A and the specificity of a bacterial α-methylcrotonyl coenzyme A carboxylase. J. Biol. Chem. 235 (1960) 3087–3092. [PMID: 13741692]
4.  Vagelos, P. Regulation of fatty acid biosynthesis. Curr. Top. Cell. Regul. 4 (1971) 119–166.
[EC 6.4.1.4 created 1961]
 
 
EC 6.4.1.5     
Accepted name: geranoyl-CoA carboxylase
Reaction: ATP + geranoyl-CoA + HCO3- = ADP + phosphate + 3-(4-methylpent-3-en-1-yl)pent-2-enedioyl-CoA
Other name(s): geranoyl coenzyme A carboxylase; geranyl-CoA carboxylase
Systematic name: geranoyl-CoA:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein. Also carboxylates dimethylpropenoyl-CoA and farnesoyl-CoA.
References:
1.  Seubert, W., Fass, E. and Remberger, U. Untersuchungen über den bakteriellen Abbau von Isoprenoiden. III. Reinigung und Eigenschaften der Geranylcarboxylase. Biochem. Z. 338 (1963) 265–275. [PMID: 14087299]
[EC 6.4.1.5 created 1972]
 
 
EC 6.4.1.6     
Accepted name: acetone carboxylase
Reaction: acetone + CO2 + ATP + 2 H2O = acetoacetate + AMP + 2 phosphate
Systematic name: acetone:carbon-dioxide ligase (AMP-forming)
Comments: Requires Mg2+ and ATP. The enzyme from Xanthobacter sp. strain Py2 also carboxylates butan-2-one to 3-oxopentanoate.
References:
1.  Sluis, M.K. and Ensign, S.A. Purification and characterization of acetone carboxylase from Xanthobacter strain Py2. Proc. Natl. Acad. Sci. USA 94 (1997) 8456–8461. [PMID: 9237998]
[EC 6.4.1.6 created 2001]
 
 
EC 6.4.1.7     
Accepted name: 2-oxoglutarate carboxylase
Reaction: ATP + 2-oxoglutarate + HCO3- = ADP + phosphate + oxalosuccinate
Glossary: oxalosuccinate = 1-oxopropane-1,2,3-tricarboxylate
Other name(s): oxalosuccinate synthetase; carboxylating factor for ICDH (incorrect); CFI; OGC
Comments: A biotin-containing enzyme that requires Mg2+ for activity. It was originally thought [1] that this enzyme was a promoting factor for the carboxylation of 2-oxoglutarate by EC 1.1.1.41, isocitrate dehydrogenase (NAD+), but this has since been disproved [2]. The product of the reaction is unstable and is quickly converted into isocitrate by the action of EC 1.1.1.41 [2].
References:
1.  Aoshima, M., Ishii, M. and Igarashi, Y. A novel biotin protein required for reductive carboxylation of 2-oxoglutarate by isocitrate dehydrogenase in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 51 (2004) 791–798. [PMID: 14731279]
2.  Aoshima, M. and Igarashi, Y. A novel oxalosuccinate-forming enzyme involved in the reductive carboxylation of 2-oxoglutarate in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 62 (2006) 748–759. [PMID: 17076668]
[EC 6.4.1.7 created 2006]
 
 
EC 6.4.1.8     
Accepted name: acetophenone carboxylase
Reaction: 2 ATP + acetophenone + HCO3- + H2O + H+ = 2 ADP + 2 phosphate + 3-oxo-3-phenylpropanoate
Systematic name: acetophenone:carbon-dioxide ligase (ADP-forming)
Comments: The enzyme is involved in anaerobic degradation of ethylbenzene. No activity with acetone, butanone, 4-hydroxy-acetophenone or 4-amino-acetophenone.
References:
1.  Jobst, B., Schuhle, K., Linne, U. and Heider, J. ATP-dependent carboxylation of acetophenone by a novel type of carboxylase. J. Bacteriol. 192 (2010) 1387–1394. [PMID: 20047908]
[EC 6.4.1.8 created 2011]
 
 
EC 6.4.1.9     
Accepted name: coenzyme F430 synthetase
Reaction: ATP + 15,173-seco-F430-173-acid = ADP + phosphate + coenzyme F430
Other name(s): cfbE (gene name)
Systematic name: 15,173-seco-F430-173-acid cyclo-ligase (ADP-forming)
Comments: The enzyme, studied from the methanogenic archaeon Methanosarcina acetivorans, catalyses the last step in the biosynthesis of the nickel-containing tetrapyrrole cofactor coenzyme F430, which is required by EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase.
References:
1.  Zheng, K., Ngo, P.D., Owens, V.L., Yang, X.P. and Mansoorabadi, S.O. The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea. Science 354 (2016) 339–342. [PMID: 27846569]
[EC 6.4.1.9 created 2017]
 
 
EC 6.5.1.1     
Accepted name: DNA ligase (ATP)
Reaction: ATP + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = [DNA ligase]-N6-(5′-adenylyl)-L-lysine + diphosphate
(1b) [DNA ligase]-N6-(5′-adenylyl)-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
Other name(s): polydeoxyribonucleotide synthase (ATP); polynucleotide ligase (ambiguous); sealase; DNA repair enzyme (ambiguous); DNA joinase (ambiguous); DNA ligase (ambiguous); deoxyribonucleic ligase (ambiguous); deoxyribonucleate ligase (ambiguous); DNA-joining enzyme (ambiguous); deoxyribonucleic-joining enzyme (ambiguous); deoxyribonucleic acid-joining enzyme (ambiguous); deoxyribonucleic repair enzyme (ambiguous); deoxyribonucleic joinase (ambiguous); deoxyribonucleic acid ligase (ambiguous); deoxyribonucleic acid joinase (ambiguous); deoxyribonucleic acid repair enzyme (ambiguous); poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming)
Systematic name: poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (ATP)
Comments: The enzyme catalyses the ligation of DNA strands with 3′-hydroxyl and 5′-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5′-phosphate terminus of the substrate, forming the capped structure 5′-(5′-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3′-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.2, DNA ligase (NAD+), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
References:
1.  Becker, A., Lyn, G., Gefter, M. and Hurwitz, J. The enzymatic repair of DNA. II. Characterization of phage-induced sealase. Proc. Natl. Acad. Sci. USA 58 (1967) 1996–2003. [PMID: 4295584]
2.  Bertazzoni, U., Mathelet, M. and Campagnari, F. Purification and properties of a polynucleotide ligase from calf thymus glands. Biochim. Biophys. Acta 287 (1972) 404–414. [PMID: 4641251]
3.  Weiss, B. and Richardson, C.C. Enzymatic breakage and joining of deoxyribonucleic acid. I. Repair of single-strand breaks in DNA by an enzyme system from Escherichia coli infected with T4 bacteriophage. Proc. Natl. Acad. Sci. USA 57 (1967) 1021–1028. [PMID: 5340583]
4.  Howes, T.R. and Tomkinson, A.E. DNA ligase I, the replicative DNA ligase. Subcell. Biochem. 62 (2012) 327–341. [PMID: 22918593]
[EC 6.5.1.1 created 1972, modified 1976, modified 2016]
 
 
EC 6.5.1.2     
Accepted name: DNA ligase (NAD+)
Reaction: NAD+ + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + β-nicotinamide D-nucleotide (overall reaction)
(1a) NAD+ + [DNA ligase]-L-lysine = [DNA ligase]-N6-(5′-adenylyl)-L-lysine + β-nicotinamide D-nucleotide
(1b) [DNA ligase]-N6-(5′-adenylyl)-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
Other name(s): polydeoxyribonucleotide synthase (NAD+); polynucleotide ligase (NAD+); DNA repair enzyme (ambiguous); DNA joinase (ambiguous); polynucleotide synthetase (nicotinamide adenine dinucleotide); deoxyribonucleic-joining enzyme (ambiguous); deoxyribonucleic ligase (ambiguous); deoxyribonucleic repair enzyme (ambiguous); deoxyribonucleic joinase (ambiguous); DNA ligase (ambiguous); deoxyribonucleate ligase (ambiguous); polynucleotide ligase (ambiguous); deoxyribonucleic acid ligase (ambiguous); polynucleotide synthetase (ambiguous); deoxyribonucleic acid joinase (ambiguous); DNA-joining enzyme (ambiguous); polynucleotide ligase (nicotinamide adenine dinucleotide); poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming, NMN-forming)
Systematic name: poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (NAD+)
Comments: The enzyme, typically found in bacteria, catalyses the ligation of DNA strands with 3′-hydroxyl and 5′-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by NAD+, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5′-phosphate terminus of the substrate, forming the capped structure 5′-(5′-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3′-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
References:
1.  Zimmerman, S.B., Little, J.W., Oshinsky, C.K. and Gellert, M. Enzymatic joining of DNA strands: a novel reaction of diphosphopyridine nucleotide. Proc. Natl. Acad. Sci. USA 57 (1967) 1841–1848. [PMID: 4291949]
2.  Little, J.W., Zimmerman, S.B., Oshinsky, C.K. and Gellert, M. Enzymatic joining of DNA strands, II. An enzyme-adenylate intermediate in the dpn-dependent DNA ligase reaction. Proc. Natl. Acad. Sci. USA 58 (1967) 2004–2011. [PMID: 4295585]
3.  Modorich, P. and Lehman, I.R. Deoxyribonucleic acid ligase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from Escherichia coli. J. Biol. Chem. 248 (1973) 7502–7511. [PMID: 4355585]
4.  Modrich, P., Anraku, Y. and Lehman, I.R. Deoxyribonucleic acid ligase. Isolation and physical characterization of the homogeneous enzyme from Escherichia coli. J. Biol. Chem. 248 (1973) 7495–7501. [PMID: 4355584]
5.  Uphoff, S., Reyes-Lamothe, R., Garza de Leon, F., Sherratt, D.J. and Kapanidis, A.N. Single-molecule DNA repair in live bacteria. Proc. Natl. Acad. Sci. USA 110 (2013) 8063–8068. [PMID: 23630273]
[EC 6.5.1.2 created 1972, modified 1976, modified 2016]
 
 
EC 6.5.1.3     
Accepted name: RNA ligase (ATP)
Reaction: ATP + (ribonucleotide)n-3′-hydroxyl + 5′-phospho-(ribonucleotide)m = (ribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [RNA ligase]-L-lysine = [RNA ligase]-N6-(5′-adenylyl)-L-lysine + diphosphate
(1b) [RNA ligase]-N6-(5′-adenylyl)-L-lysine + 5′-phospho-(ribonucleotide)m = 5′-(5′-diphosphoadenosine)-(ribonucleotide)m + [RNA ligase]-L-lysine
(1c) (ribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(ribonucleotide)m = (ribonucleotide)n+m + AMP
Other name(s): polyribonucleotide synthase (ATP); RNA ligase; polyribonucleotide ligase; ribonucleic ligase; poly(ribonucleotide):poly(ribonucleotide) ligase (AMP-forming)
Systematic name: poly(ribonucleotide)-3′-hydroxyl:5′-phospho-poly(ribonucleotide) ligase (ATP)
Comments: The enzyme catalyses the ligation of RNA strands with 3′-hydroxyl and 5′-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in RNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5′-phosphate terminus of the substrate, forming the capped structure 5′-(5′-diphosphoadenosine)-[RNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3′-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate.
References:
1.  Silber, R., Malathi, V.G. and Hurwitz, J. Purification and properties of bacteriophage T4-induced RNA ligase. Proc. Natl. Acad. Sci. USA 69 (1972) 3009–3013. [PMID: 4342972]
2.  Cranston, J.W., Silber, R., Malathi, V.G. and Hurwitz, J. Studies on ribonucleic acid ligase. Characterization of an adenosine triphosphate-inorganic pyrophosphate exchange reaction and demonstration of an enzyme-adenylate complex with T4 bacteriophage-induced enzyme. J. Biol. Chem. 249 (1974) 7447–7456. [PMID: 4373468]
3.  Sugino, A., Snoper, T.J. and Cozzarelli, N.R. Bacteriophage T4 RNA ligase. Reaction intermediates and interaction of substrates. J. Biol. Chem. 252 (1977) 1732–1738. [PMID: 320212]
4.  Romaniuk, P.J. and Uhlenbeck, O.C. Joining of RNA molecules with RNA ligase. Methods Enzymol. 100 (1983) 52–59. [PMID: 6194411]
5.  Ho, C.K., Wang, L.K., Lima, C.D. and Shuman, S. Structure and mechanism of RNA ligase. Structure 12 (2004) 327–339. [PMID: 14962393]
6.  Nandakumar, J., Shuman, S. and Lima, C.D. RNA ligase structures reveal the basis for RNA specificity and conformational changes that drive ligation forward. Cell 127 (2006) 71–84. [PMID: 17018278]
[EC 6.5.1.3 created 1976, modified 2016]
 
 
EC 6.5.1.4     
Accepted name: RNA 3′-terminal-phosphate cyclase (ATP)
Reaction: ATP + [RNA]-3′-(3′-phospho-ribonucleoside) = AMP + diphosphate + [RNA]-3′-(2′,3′-cyclophospho)-ribonucleoside (overall reaction)
(1a) ATP + [RNA 3′-phosphate cyclase]-L-histidine = [RNA 3′-phosphate cyclase]-Nτ-(5′-adenylyl)-L-histidine + diphosphate
(1b) [RNA 3′-phosphate cyclase]-Nτ-(5′-adenylyl)-L-histidine + [RNA]-3′-(3′-phospho-ribonucleoside) = [RNA 3′-phosphate cyclase]-L-histidine + [RNA]-3′-ribonucleoside-3′-(5′-diphosphoadenosine)
(1c) [RNA]-3′-ribonucleoside-3′-(5′-diphosphoadenosine) = [RNA]-3′-(2′,3′-cyclophospho)-ribonucleoside + AMP
Other name(s): rtcA (gene name); RNA cyclase (ambiguous); RNA-3′-phosphate cyclase (ambiguous)
Systematic name: RNA-3′-phosphate:RNA ligase (cyclizing, AMP-forming)
Comments: The enzyme converts the 3′-terminal phosphate of various RNA substrates into the 2′,3′-cyclic phosphodiester in an ATP-dependent reaction. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a histidine residue [5,6]. The adenylate group is then transferred to the 3′-phosphate terminus of the substrate, forming the capped structure [RNA]-3′-(5′-diphosphoadenosine). Finally, the enzyme catalyses an attack of the vicinal O-2′ on the 3′-phosphorus, which results in formation of cyclic phosphate and release of the adenylate. The enzyme also has a polynucleotide 5′ adenylylation activity [7]. cf. EC 6.5.1.5, RNA 3′-terminal-phosphate cyclase (GTP).
References:
1.  Filipowicz, W., Konarska, M., Gross, H.J. and Shatkin, A.J. RNA 3′-terminal phosphate cyclase activity and RNA ligation in HeLa cell extract. Nucleic Acids Res. 11 (1983) 1405–1418. [PMID: 6828385]
2.  Reinberg, D., Arenas, J. and Hurwitz, J. The enzymatic conversion of 3′-phosphate terminated RNA chains to 2′,3′-cyclic phosphate derivatives. J. Biol. Chem. 260 (1985) 6088–6097. [PMID: 2581947]
3.  Genschik, P., Billy, E., Swianiewicz, M. and Filipowicz, W. The human RNA 3′-terminal phosphate cyclase is a member of a new family of proteins conserved in Eucarya, Bacteria and Archaea. EMBO J. 16 (1997) 2955–2967. [PMID: 9184239]
4.  Genschik, P., Drabikowski, K. and Filipowicz, W. Characterization of the Escherichia coli RNA 3′-terminal phosphate cyclase and its σ54-regulated operon. J. Biol. Chem. 273 (1998) 25516–25526. [PMID: 9738023]
5.  Billy, E., Hess, D., Hofsteenge, J. and Filipowicz, W. Characterization of the adenylation site in the RNA 3′-terminal phosphate cyclase from Escherichia coli. J. Biol. Chem. 274 (1999) 34955–34960. [PMID: 10574971]
6.  Tanaka, N. and Shuman, S. Structure-activity relationships in human RNA 3′-phosphate cyclase. RNA 15 (2009) 1865–1874. [PMID: 19690099]
7.  Chakravarty, A.K. and Shuman, S. RNA 3′-phosphate cyclase (RtcA) catalyzes ligase-like adenylylation of DNA and RNA 5′-monophosphate ends. J. Biol. Chem. 286 (2011) 4117–4122. [PMID: 21098490]
8.  Das, U. and Shuman, S. 2′-Phosphate cyclase activity of RtcA: a potential rationale for the operon organization of RtcA with an RNA repair ligase RtcB in Escherichia coli and other bacterial taxa. RNA 19 (2013) 1355–1362. [PMID: 23945037]
[EC 6.5.1.4 created 1986, modified 1989, modified 2013, modified 2016]
 
 
EC 6.5.1.5     
Accepted name: RNA 3′-terminal-phosphate cyclase (GTP)
Reaction: GTP + [RNA]-3′-(3′-phospho-ribonucleoside) = GMP + diphosphate + [RNA]-3′-(2′,3′-cyclophospho)-ribonucleoside (overall reaction)
(1a) GTP + [RNA 3′-phosphate cyclase]-L-histidine = 5′-guanosyl [RNA 3′-phosphate cyclase]-Nτ-phosphono-L-histidine + diphosphate
(1b) 5′-guanosyl [RNA 3′-phosphate cyclase]-Nτ-phosphono-L-histidine + [RNA]-3′-(3′-phospho-ribonucleoside) = [RNA 3′-phosphate cyclase]-L-histidine + [RNA]-3′-ribonucleoside-3′-(5′-diphosphoguanosine)
(1c) [RNA]-3′-ribonucleoside-3′-(5′-diphosphoguanosine) = [RNA]-3′-(2′,3′-cyclophospho)-ribonucleoside + GMP
Other name(s): Pf-Rtc; RNA-3′-phosphate cyclase (GTP)
Systematic name: RNA-3′-phosphate:RNA ligase (cyclizing, GMP-forming)
Comments: The enzyme, which is specific for GTP, was characterized from the archaeon Pyrococcus furiosus. The enzyme converts the 3′-terminal phosphate of various RNA substrates into the 2′,3′-cyclic phosphodiester in a GTP-dependent reaction. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by GTP, forming a phosphoramide bond between guanylate and a histidine residue. The guanylate group is then transferred to the 3′-phosphate terminus of the substrate, forming the capped structure [RNA]-3′-(5′-diphosphoguanosine). Finally, the enzyme catalyses an attack of the vicinal O-2′ on the 3′-phosphorus, which results in formation of cyclic phosphate and release of the guanylate. cf. EC 6.5.1.4, RNA-3′-phosphate cyclase (ATP).
References:
1.  Sato, A., Soga, T., Igarashi, K., Takesue, K., Tomita, M. and Kanai, A. GTP-dependent RNA 3′-terminal phosphate cyclase from the hyperthermophilic archaeon Pyrococcus furiosus. Genes Cells 16 (2011) 1190–1199. [PMID: 22074260]
[EC 6.5.1.5 created 2013, modified 2016]
 
 
EC 6.5.1.6     
Accepted name: DNA ligase (ATP or NAD+)
Reaction: (1) ATP + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + diphosphate
(1b) 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
(2) NAD+ + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + β-nicotinamide D-nucleotide (overall reaction)
(2a) NAD+ + [DNA ligase]-L-lysine = 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + β-nicotinamide D-nucleotide
(2b) 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(2c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
Systematic name: poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (ATP or NAD+)
Comments: The enzymes from the archaea Thermococcus fumicolans and Thermococcus onnurineus show high activity with either ATP or NAD+, and significantly lower activity with TTP, GTP, and CTP. The enzyme catalyses the ligation of DNA strands with 3′-hydroxyl and 5′-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP or NAD+, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5′-phosphate terminus of the substrate, forming the capped structure 5′-(5′-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3′-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. Different from EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.2, DNA ligase (NAD+) and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
References:
1.  Rolland, J.L., Gueguen, Y., Persillon, C., Masson, J.M. and Dietrich, J. Characterization of a thermophilic DNA ligase from the archaeon Thermococcus fumicolans. FEMS Microbiol. Lett. 236 (2004) 267–273. [PMID: 15251207]
2.  Kim, Y.J., Lee, H.S., Bae, S.S., Jeon, J.H., Yang, S.H., Lim, J.K., Kang, S.G., Kwon, S.T. and Lee, J.H. Cloning, expression, and characterization of a DNA ligase from a hyperthermophilic archaeon Thermococcus sp. Biotechnol. Lett. 28 (2006) 401–407. [PMID: 16614906]
[EC 6.5.1.6 created 2014, modified 2016]
 
 
EC 6.5.1.7     
Accepted name: DNA ligase (ATP, ADP or GTP)
Reaction: (1) ATP + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + diphosphate
(1b) 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
(2) ADP + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + phosphate (overall reaction)
(2a) ADP + [DNA ligase]-L-lysine = 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + phosphate
(2b) 5′-adenosyl [DNA ligase]-Nε-phosphono-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(2c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
(3) GTP + (deoxyribonucleotide)n-3′-hydroxyl + 5′-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + GMP + diphosphate (overall reaction)
(3a) GTP + [DNA ligase]-L-lysine = 5′-guanosyl [DNA ligase]-Nε-phosphono-L-lysine + diphosphate
(3b) 5′-guanosyl [DNA ligase]-Nε-phosphono-L-lysine + 5′-phospho-(deoxyribonucleotide)m = 5′-(5′-diphosphoguanosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(3c) (deoxyribonucleotide)n-3′-hydroxyl + 5′-(5′-diphosphoguanosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + GMP
Other name(s): poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (ATP, ADP or GTP)
Systematic name: poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (ATP, ADP or GTP)
Comments: The enzymes from the archaea Hyperthermus butylicus and Sulfophobococcus zilligii are active with ATP, ADP or GTP. They show no activity with NAD+. The enzyme catalyses the ligation of DNA strands with 3′-hydroxyl and 5′-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, ADP, or GTP, forming a phosphoramide bond between adenylate/guanylate and a lysine residue. The nucleotide is then transferred to the 5′-phosphate terminus of the substrate, forming the capped structure 5′-(5′-diphosphoadenosine/guanosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3′-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the nucleotide. Different from EC 6.5.1.1, DNA ligase (ATP), and EC 6.5.1.6, DNA ligase (ATP or NAD+), which cannot utilize GTP.
References:
1.  Sun, Y., Seo, M.S., Kim, J.H., Kim, Y.J., Kim, G.A., Lee, J.I., Lee, J.H. and Kwon, S.T. Novel DNA ligase with broad nucleotide cofactor specificity from the hyperthermophilic crenarchaeon Sulfophobococcus zilligii: influence of ancestral DNA ligase on cofactor utilization. Environ Microbiol 10 (2008) 3212–3224. [PMID: 18647334]
2.  Kim, J.H., Lee, K.K., Sun, Y., Seo, G.J., Cho, S.S., Kwon, S.H. and Kwon, S.T. Broad nucleotide cofactor specificity of DNA ligase from the hyperthermophilic crenarchaeon Hyperthermus butylicus and its evolutionary significance. Extremophiles 17 (2013) 515–522. [PMID: 23546841]
[EC 6.5.1.7 created 2014, modified 2016]
 
 
EC 6.5.1.8     
Accepted name: 3′-phosphate/5′-hydroxy nucleic acid ligase
Reaction: (1) (ribonucleotide)n-3′-phosphate + 5′-hydroxy-(ribonucleotide)m + GTP = (ribonucleotide)n+m + GMP + diphosphate (overall reaction)
(1a) GTP + [RNA ligase]-L-histidine = [RNA ligase]-Nτ-(5′-guanosyl-phosphono)-L-histidine + diphosphate
(1b) [RNA ligase]-Nτ-(5′-guanosyl-phosphono)-L-histidine + (ribonucleotide)n-3′-phosphate = (ribonucleotide)n-3′-(5′-diphosphoguanosine) + [RNA ligase]-L-histidine
(1c) (ribonucleotide)n-3′-(5′-diphosphoguanosine) + 5′-hydroxy-(ribonucleotide)m = (ribonucleotide)n+m + GMP
(2) (ribonucleotide)n-2′,3′-cyclophosphate + 5′-hydroxy-(ribonucleotide)m + GTP + H2O = (ribonucleotide)n+m + GMP + diphosphate (overall reaction)
(2a) (ribonucleotide)n-2′,3′-cyclophosphate + H2O = (ribonucleotide)n-3′-phosphate
(2b) GTP + [RNA ligase]-L-histidine = [RNA ligase]-Nτ-(5′-guanosyl-phosphono)-L-histidine + diphosphate
(2c) [RNA ligase]-Nτ-(5′-guanosyl-phosphono)-L-histidine + (ribonucleotide)n-3′-phosphate = (ribonucleotide)n-3′-(5′-diphosphoguanosine) + [RNA ligase]-L-histidine
(2d) (ribonucleotide)n-3′-(5′-diphosphoguanosine) + 5′-hydroxy-(ribonucleotide)m = (ribonucleotide)n+m + GMP
Other name(s): rtcB (gene name)
Systematic name: poly(ribonucleotide)-3′-phosphate:5′-hydroxy-poly(ribonucleotide) ligase (GMP-forming)
Comments: The enzyme is a GTP- and Mn2+-dependent 3′-5′ nucleic acid ligase with the ability to join RNA with 3′-phosphate or 2′,3′-cyclic-phosphate ends to RNA with 5′-hydroxy ends. It can also join DNA with 3′-phosphate ends to DNA with 5′-hydroxy ends, provided the DNA termini are unpaired [6]. The enzyme is found in members of all three kingdoms of life, and is essential in metazoa for the splicing of intron-containing tRNAs. The reaction follows a three-step mechanism with initial activation of the enzyme by GTP hydrolysis, forming a phosphoramide bond between the guanylate and a histidine residue. The guanylate group is transferred to the 3′-phosphate terminus of the substrate, forming the capped structure [DNA/RNA]-3′-(5′-diphosphoguanosine). When a suitable 5′-OH end is available, the enzyme catalyses an attack of the 5′-OH on the capped end to form a 3′-5′ phosphodiester splice junction, releasing the guanylate. When acting on an RNA 2′,3′-cyclic-phosphate, the enzyme catalyses an additional reaction, hydrolysing the cyclic phosphate to a 3′-phosphate [9]. The metazoan enzyme requires activating cofactors in order to achieve multiple turnover catalysis [8].
References:
1.  Tanaka, N., Meineke, B. and Shuman, S. RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo. J. Biol. Chem. 286 (2011) 30253–30257. [PMID: 21757685]
2.  Tanaka, N. and Shuman, S. RtcB is the RNA ligase component of an Escherichia coli RNA repair operon. J. Biol. Chem. 286 (2011) 7727–7731. [PMID: 21224389]
3.  Tanaka, N., Chakravarty, A.K., Maughan, B. and Shuman, S. Novel mechanism of RNA repair by RtcB via sequential 2′,3′-cyclic phosphodiesterase and 3′-phosphate/5′-hydroxyl ligation reactions. J. Biol. Chem. 286 (2011) 43134–43143. [PMID: 22045815]
4.  Desai, K.K. and Raines, R.T. tRNA ligase catalyzes the GTP-dependent ligation of RNA with 3′-phosphate and 5′-hydroxyl termini. Biochemistry 51 (2012) 1333–1335. [PMID: 22320833]
5.  Chakravarty, A.K., Subbotin, R., Chait, B.T. and Shuman, S. RNA ligase RtcB splices 3′-phosphate and 5′-OH ends via covalent RtcB-(histidinyl)-GMP and polynucleotide-(3′)pp(5′)G intermediates. Proc. Natl. Acad. Sci. USA 109 (2012) 6072–6077. [PMID: 22474365]
6.  Chakravarty, A.K. and Shuman, S. The sequential 2′,3′-cyclic phosphodiesterase and 3′-phosphate/5′-OH ligation steps of the RtcB RNA splicing pathway are GTP-dependent. Nucleic Acids Res. 40 (2012) 8558–8567. [PMID: 22730297]
7.  Das, U., Chakravarty, A.K., Remus, B.S. and Shuman, S. Rewriting the rules for end joining via enzymatic splicing of DNA 3′-PO4 and 5′-OH ends. Proc. Natl. Acad. Sci. USA 110 (2013) 20437–20442. [PMID: 24218597]
8.  Desai, K.K., Beltrame, A.L. and Raines, R.T. Coevolution of RtcB and Archease created a multiple-turnover RNA ligase. RNA 21 (2015) 1866–1872. [PMID: 26385509]
9.  Maughan, W.P. and Shuman, S. Distinct contributions of enzymic functional groups to the 2′,3′-cyclic phosphodiesterase, 3′-phosphate guanylylation, and 3′-ppG/5′-OH ligation steps of the Escherichia coli RtcB nucleic acid splicing pathway. J. Bacteriol. 198 (2016) 1294–1304. [PMID: 26858100]
[EC 6.5.1.8 created 2017]
 
 
EC 6.6.1.1     
Accepted name: magnesium chelatase
Reaction: ATP + protoporphyrin IX + Mg2+ + H2O = ADP + phosphate + Mg-protoporphyrin IX + 2 H+
Other name(s): protoporphyrin IX magnesium-chelatase; protoporphyrin IX Mg-chelatase; magnesium-protoporphyrin IX chelatase; magnesium-protoporphyrin chelatase; magnesium-chelatase; Mg-chelatase; Mg-protoporphyrin IX magnesio-lyase
Systematic name: Mg-protoporphyrin IX magnesium-lyase
Comments: This is the first committed step of chlorophyll biosynthesis and is a branchpoint of two major routes in the tetrapyrrole pathway.
References:
1.  Walker, C.J. and Weinstein, J.D. In vitro assay of the chlorophyll biosynthetic enzyme Mg-chelatase: resolution of the activity into soluble and membrane-bound fractions. Proc. Natl. Acad. Sci. USA 88 (1991) 5789–5793. [PMID: 11607197]
2.  Walker, C.J. and Willows, R.D. Mechanism and regulation of Mg-chelatase. Biochem. J. 327 (1997) 321–333. [PMID: 9359397]
3.  Fodje, M.N., Hansson, A., Hansson, M., Olsen, J.G., Gough, S., Willows, R.D. and Al-Karadaghi, S. Interplay between an AAA module and an integrin I domain may regulate the function of magnesium chelatase. J. Mol. Biol. 311 (2001) 111–122. [PMID: 11469861]
[EC 6.6.1.1 created 2003]
 
 
EC 6.6.1.2     
Accepted name: cobaltochelatase
Reaction: ATP + hydrogenobyrinic acid a,c-diamide + Co2+ + H2O = ADP + phosphate + cob(II)yrinic acid a,c-diamide + H+
Other name(s): hydrogenobyrinic acid a,c-diamide cobaltochelatase; CobNST; CobNCobST
Systematic name: hydrogenobyrinic-acid-a,c-diamide:cobalt cobalt-ligase (ADP-forming)
Comments: This enzyme, which forms part of the aerobic cobalamin biosynthesis pathway, is a type I chelatase, being heterotrimeric and ATP-dependent. It comprises two components, one of which corresponds to CobN and the other is composed of two polypeptides, specified by cobS and cobT in Pseudomonas denitrificans, and named CobST [1]. Hydrogenobyrinic acid is a very poor substrate. ATP can be replaced by dATP or CTP but the reaction proceeds more slowly. CobN exhibits a high affinity for hydrogenobyrinic acid a,c-diamide. The oligomeric protein CobST possesses at least one sulfhydryl group that is essential for ATP-binding. Once the Co2+ is inserted, the next step in the pathway ensures that the cobalt is ligated securely by reducing Co(II) to Co(I). This step is carried out by EC 1.16.8.1, cob(II)yrinic acid a,c-diamide reductase.
References:
1.  Debussche, L., Couder, M., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Assay, purification, and characterization of cobaltochelatase, a unique complex enzyme catalyzing cobalt insertion in hydrogenobyrinic acid a,c-diamide during coenzyme B12 biosynthesis in Pseudomonas denitrificans. J. Bacteriol. 174 (1992) 7445–7451. [PMID: 1429466]
2.  Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390–412. [PMID: 12195810]
[EC 6.6.1.2 created 2004]
 
 


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