The Enzyme Database

Displaying entries 101-150 of 262.

<< Previous | Next >>    printer_iconPrintable version

EC 6.2.1.70     
Accepted name: L-threonine—[L-threonyl-carrier protein] ligase
Reaction: ATP + L-threonine + holo-[L-threonyl-carrier protein] = AMP + diphosphate + L-threonyl-[L-threonyl-carrier protein] (overall reaction)
(1a) ATP + L-threonine = diphosphate + (L-threonyl)adenylate
(1b) (L-threonyl)adenylate + holo-[L-threonyl-carrier protein] = AMP + L-threonyl-[L-threonyl-carrier protein]
Other name(s): dhbF (gene name); pmsD (gene name); syrB1 (gene name)
Systematic name: L-threonine:[L-threonyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-threonine to (L-threonyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein (as in the case of DhbF in bacillibactin biosynthesis), or of a different protein (as in the case of PmsD in pseudomonine biosynthesis). This activity is often found as part of a larger non-ribosomal peptide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Vaillancourt, F.H., Yin, J. and Walsh, C.T. SyrB2 in syringomycin E biosynthesis is a nonheme FeII α-ketoglutarate- and O2-dependent halogenase. Proc. Natl. Acad. Sci. USA 102 (2005) 10111–10116. [DOI] [PMID: 16002467]
2.  Sattely, E.S. and Walsh, C.T. A latent oxazoline electrophile for N-O-C bond formation in pseudomonine biosynthesis. J. Am. Chem. Soc. 130 (2008) 12282–12284. [DOI] [PMID: 18710233]
[EC 6.2.1.70 created 2021]
 
 
EC 6.2.1.71     
Accepted name: 2,3-dihydroxybenzoate—[aryl-carrier protein] ligase
Reaction: ATP + 2,3-dihydroxybenzoate + holo-[aryl-carrier protein] = AMP + diphosphate + 2,3-dihydroxybenzoyl-[aryl-carrier protein] (overall reaction)
(1a) ATP + 2,3-dihydroxybenzoate = diphosphate + (2,3-dihydroxybenzoyl)adenylate
(1b) (2,3-dihydroxybenzoyl)adenylate + holo-[aryl-carrier protein] = AMP + 2,3-dihydroxybenzoyl-[aryl-carrier protein]
Other name(s): entE (gene name); vibE (gene name); dhbE (gene name); angE (gene name)
Systematic name: 2,3-dihydroxybenzoate:[aryl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of 2,3-dihydroxybenzoate to (2,3-dihydroxybenzoyl)adenylate, followed by the transfer the activated compound to the free thiol of a phosphopantetheine arm of an aryl-carrier protein domain of a specific non-ribosomal peptide synthase. For example, the EntE enzyme of Escherichia coli is part of the enterobactin synthase complex, the VibE enzyme of Vibrio cholerae is part of the vibriobactin synthase complex, and the DhbE enzyme of Bacillus subtilis is part of the bacillibactin synthase complex.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Gehring, A.M., Bradley, K.A. and Walsh, C.T. Enterobactin biosynthesis in Escherichia coli: isochorismate lyase (EntB) is a bifunctional enzyme that is phosphopantetheinylated by EntD and then acylated by EntE using ATP and 2,3-dihydroxybenzoate. Biochemistry 36 (1997) 8495–8503. [DOI] [PMID: 9214294]
2.  Wyckoff, E.E., Stoebner, J.A., Reed, K.E. and Payne, S.M. Cloning of a Vibrio cholerae vibriobactin gene cluster: identification of genes required for early steps in siderophore biosynthesis. J. Bacteriol. 179 (1997) 7055–7062. [PMID: 9371453]
3.  Ehmann, D.E., Shaw-Reid, C.A., Losey, H.C. and Walsh, C.T. The EntF and EntE adenylation domains of Escherichia coli enterobactin synthetase: sequestration and selectivity in acyl-AMP transfers to thiolation domain cosubstrates. Proc. Natl. Acad. Sci. USA 97 (2000) 2509–2514. [DOI] [PMID: 10688898]
4.  Keating, T.A., Marshall, C.G. and Walsh, C.T. Vibriobactin biosynthesis in Vibrio cholerae: VibH is an amide synthase homologous to nonribosomal peptide synthetase condensation domains. Biochemistry 39 (2000) 15513–15521. [PMID: 11112537]
5.  May, J.J., Wendrich, T.M. and Marahiel, M.A. The dhb operon of Bacillus subtilis encodes the biosynthetic template for the catecholic siderophore 2,3-dihydroxybenzoate-glycine-threonine trimeric ester bacillibactin. J. Biol. Chem. 276 (2001) 7209–7217. [DOI] [PMID: 11112781]
6.  Sikora, A.L., Wilson, D.J., Aldrich, C.C. and Blanchard, J.S. Kinetic and inhibition studies of dihydroxybenzoate-AMP ligase from Escherichia coli. Biochemistry 49 (2010) 3648–3657. [DOI] [PMID: 20359185]
7.  Khalil, S. and Pawelek, P.D. Enzymatic adenylation of 2,3-dihydroxybenzoate is enhanced by a protein-protein interaction between Escherichia coli 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase (EntA) and 2,3-dihydroxybenzoate-AMP ligase (EntE). Biochemistry 50 (2011) 533–545. [DOI] [PMID: 21166461]
[EC 6.2.1.71 created 2021 (EC 2.7.7.58 created 1992, incorporated 2021)]
 
 
EC 6.2.1.72     
Accepted name: L-serine—[L-seryl-carrier protein] ligase
Reaction: ATP + L-serine + holo-[L-seryl-carrier protein] = AMP + diphosphate + L-seryl-[L-seryl-carrier protein] (overall reaction)
(1a) ATP + L-serine = diphosphate + (L-seryl)adenylate
(1b) (L-seryl)adenylate + holo-[L-seryl-carrier protein] = AMP + L-seryl-[L-seryl-carrier protein]
Other name(s): entF (gene name); zmaJ (gene name); gdnB (gene name); serine-activating enzyme
Systematic name: L-serine:[L-seryl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-serine to (L-seryl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein, or of a different protein. This activity is often found as part of a larger non-ribosomal peptide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Pettis, G.S. and McIntosh, M.A. Molecular characterization of the Escherichia coli enterobactin cistron entF and coupled expression of entF and the fes gene. J. Bacteriol. 169 (1987) 4154–4162. [PMID: 3040679]
2.  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]
3.  Reichert, J., Sakaitani, M. and Walsh, C.T. Characterization of EntF as a serine-activating enzyme. Protein Sci. 1 (1992) 549–556. [DOI] [PMID: 1338974]
4.  Ehmann, D.E., Shaw-Reid, C.A., Losey, H.C. and Walsh, C.T. The EntF and EntE adenylation domains of Escherichia coli enterobactin synthetase: sequestration and selectivity in acyl-AMP transfers to thiolation domain cosubstrates. Proc. Natl. Acad. Sci. USA 97 (2000) 2509–2514. [DOI] [PMID: 10688898]
5.  Chan, Y.A., Boyne, M.T., 2nd, Podevels, A.M., Klimowicz, A.K., Handelsman, J., Kelleher, N.L. and Thomas, M.G. Hydroxymalonyl-acyl carrier protein (ACP) and aminomalonyl-ACP are two additional type I polyketide synthase extender units. Proc. Natl. Acad. Sci. USA 103 (2006) 14349–14354. [DOI] [PMID: 16983083]
6.  Frueh, D.P., Arthanari, H., Koglin, A., Vosburg, D.A., Bennett, A.E., Walsh, C.T. and Wagner, G. Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase. Nature 454 (2008) 903–906. [DOI] [PMID: 18704088]
[EC 6.2.1.72 created 2021]
 
 
EC 6.2.1.73     
Accepted name: L-tryptophan—[L-tryptophyl-carrier protein] ligase
Reaction: ATP + L-tryptophan + holo-[L-tryptophyl-carrier protein] = AMP + diphosphate + -L-tryptophyl-[L-tryptophyl-carrier protein] (overall reaction)
(1a) ATP + tryptophan = diphosphate + (L-tryptophyl)adenylate
(1b) (L-tryptophyl)adenylate + holo-[L-tryptophyl-carrier protein] = AMP + L-tryptophyl-[L-tryptophyl-carrier protein]
Other name(s): ecm13 (gene name); swb11 (gene name)
Systematic name: L-tryptophan:[L-tryptophyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-tryptophan to (L-tryptophyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein, or of a different protein. This activity is often found as part of a larger non-ribosomal peptide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Zhang, C., Kong, L., Liu, Q., Lei, X., Zhu, T., Yin, J., Lin, B., Deng, Z. and You, D. In vitro characterization of echinomycin biosynthesis: formation and hydroxylation of L-tryptophanyl-S-enzyme and oxidation of (2S,3S) β-hydroxytryptophan. PLoS One 8:e56772 (2013). [DOI] [PMID: 23437232]
[EC 6.2.1.73 created 2021]
 
 
EC 6.2.1.74     
Accepted name: 3-amino-5-hydroxybenzoate—[acyl-carrier protein] ligase
Reaction: ATP + 3-amino-5-hydroxybenzoate + a holo-[acyl-carrier protein] = 3-amino-5-hydroxybenzoyl-[acyl-carrier protein] + AMP + diphosphate
Other name(s): rifA (gene name); mitE (gene name)
Systematic name: 3-amino-5-hydroxybenzoate:[acyl carrier protein] ligase (AMP-forming)
Comments: During the biosynthesis of most ansamycin antibiotics such as rifamycins, streptovaricins, naphthomycins, and chaxamycins, the activity is catalysed by the loading domain of the respective polyketide synthase (PKS), which transfers the substrate to the acyl-carrier protein domain of the first extension module of the PKS. During the biosynthesis of the mitomycins the reaction is catalysed by the MitE protein, which transfers the substrate to a dedicated acyl-carrier protein (MmcB).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Admiraal, S.J., Walsh, C.T. and Khosla, C. The loading module of rifamycin synthetase is an adenylation-thiolation didomain with substrate tolerance for substituted benzoates. Biochemistry 40 (2001) 6116–6123. [PMID: 11352749]
2.  Admiraal, S.J., Khosla, C. and Walsh, C.T. The loading and initial elongation modules of rifamycin synthetase collaborate to produce mixed aryl ketide products. Biochemistry 41 (2002) 5313–5324. [PMID: 11955082]
3.  Admiraal, S.J., Khosla, C. and Walsh, C.T. A Switch for the transfer of substrate between nonribosomal peptide and polyketide modules of the rifamycin synthetase assembly line. J. Am. Chem. Soc. 125 (2003) 13664–13665. [DOI] [PMID: 14599196]
4.  Chamberland, S., Gruschow, S., Sherman, D.H. and Williams, R.M. Synthesis of potential early-stage intermediates in the biosynthesis of FR900482 and mitomycin C. Org. Lett. 11 (2009) 791–794. [DOI] [PMID: 19161340]
[EC 6.2.1.74 created 2021]
 
 
EC 6.2.1.75     
Accepted name: indoleacetate—CoA ligase
Reaction: ATP + (indol-3-yl)acetate + CoA = AMP + diphosphate + (indol-3-yl)acetyl-CoA
Other name(s): iaaB (gene name)
Systematic name: (indol-3-yl)acetate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Aromatoleum aromaticum, is involved in degradation of (indol-3-yl)acetate. It is also active with phenylacetate and the non-physiological compound (2-naphthyl)acetate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Schuhle, K., Nies, J. and Heider, J. An indoleacetate-CoA ligase and a phenylsuccinyl-CoA transferase involved in anaerobic metabolism of auxin. Environ. Microbiol. 18 (2016) 3120–3132. [DOI] [PMID: 27102732]
[EC 6.2.1.75 created 2022]
 
 
EC 6.2.1.76     
Accepted name: malonate—CoA ligase
Reaction: ATP + malonate + CoA = AMP + diphosphate + malonyl-CoA
Other name(s): ACSF3 (gene name); AAE13 (gene name); malonyl-CoA synthetase
Systematic name: malonate:CoA ligase (AMP-forming)
Comments: The enzyme, found in mitochondria, detoxifies malonate, which is a potent inhibitor of mitochondrial respiration, and provides malonyl-CoA to the mitochondrial fatty acid biosynthesis pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Gueguen, V., Macherel, D., Jaquinod, M., Douce, R. and Bourguignon, J. Fatty acid and lipoic acid biosynthesis in higher plant mitochondria. J. Biol. Chem. 275 (2000) 5016–5025. [DOI] [PMID: 10671542]
2.  Witkowski, A., Thweatt, J. and Smith, S. Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis. J. Biol. Chem. 286 (2011) 33729–33736. [DOI] [PMID: 21846720]
3.  Chen, H., Kim, H.U., Weng, H. and Browse, J. Malonyl-CoA synthetase, encoded by Acyl Activating Enzyme13, is essential for growth and development of Arabidopsis. Plant Cell 23 (2011) 2247–2262. [DOI] [PMID: 21642549]
4.  Guan, X. and Nikolau, B.J. AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis. Plant J. 85 (2016) 581–593. [DOI] [PMID: 26836315]
5.  Bowman, C.E., Rodriguez, S., Selen Alpergin, E.S., Acoba, M.G., Zhao, L., Hartung, T., Claypool, S.M., Watkins, P.A. and Wolfgang, M.J. The mammalian malonyl-CoA synthetase ACSF3 is required for mitochondrial protein malonylation and metabolic efficiency. Cell Chem. Biol. 24 (2017) 673–684.e4. [DOI] [PMID: 28479296]
6.  Bowman, C.E. and Wolfgang, M.J. Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Adv Biol Regul 71 (2019) 34–40. [DOI] [PMID: 30201289]
[EC 6.2.1.76 created 2022]
 
 
EC 6.2.2.1     
Accepted name: thioglycine synthase
Reaction: ATP + sulfide + a [methyl-coenzyme M reductase]-glycine = ADP + phosphate + a [methyl-coenzyme M reductase]-thioglycine
Glossary: thioglycine = 2-aminoethanethioic O-acid
Other name(s): ycaO (gene name) (ambiguous)
Systematic name: [methyl-coenzyme M reductase]-glycine—sulfur ligase (thioglycine-forming)
Comments: Requires Mg2+. The enzyme is found in anaerobic methanogenic and methanotrophic archaea, where it modifies a glycine residue in EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase (methyl-CoM reductase). Upon binding to its substrate, an external source of sulfide attacks the target amide bond generating a tetrahedral intermediate. The amide oxyanion attacks the γ-phosphate of ATP, releasing ADP and forming a phosphorylated thiolate intermediate that collapses to form thioglycine and phosphate. In most organisms activity requires a second protein (TfuA) , which may allosterically activate this enzyme or assist in the delivery of sulfide to the substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Nayak, D.D., Mahanta, N., Mitchell, D.A. and Metcalf, W.W. Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea. Elife 6:e29218 (2017). [PMID: 28880150]
2.  Mahanta, N., Liu, A., Dong, S., Nair, S.K. and Mitchell, D.A. Enzymatic reconstitution of ribosomal peptide backbone thioamidation. Proc. Natl. Acad. Sci. USA 115 (2018) 3030–3035. [PMID: 29507203]
3.  Dong, S.H., Liu, A., Mahanta, N., Mitchell, D.A. and Nair, S.K. Mechanistic basis for ribosomal peptide backbone modifications. ACS Cent. Sci. 5 (2019) 842–851. [PMID: 31139720]
[EC 6.2.2.1 created 2020]
 
 
EC 6.2.2.2     
Accepted name: oxazoline synthase
Reaction: (1) ATP + a [protein]-(L-amino acyl-L-serine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-2-oxazoline
(2) ATP + a [protein]-(L-amino acyl-L-threonine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-2-oxazoline
(3) ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Other name(s): cyanobactin heterocyclase; cyanobactin cyclodehydratase; patD (gene name); balhD (gene name); micD (gene name)
Systematic name: [protein]-(L-amino acyl-L-serine) cyclodehydratase (2-oxazoline-forming)
Comments: Requires Mg2+. The enzyme, which participates in the biosynthesis of ribosomal peptide natural products (RiPPs), converts L-cysteine, L-serine and L-threonine residues to thiazoline, oxazoline, and methyloxazoline rings, respectively. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089–4091. [PMID: 20210311]
2.  Melby, J.O., Dunbar, K.L., Trinh, N.Q. and Mitchell, D.A. Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase. J. Am. Chem. Soc. 134 (2012) 5309–5316. [PMID: 22401305]
3.  Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125–2132. [PMID: 30912640]
[EC 6.2.2.2 created 2020]
 
 
EC 6.2.2.3     
Accepted name: thiazoline synthase
Reaction: ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Glossary: L-cysteine heterocyclase; truD (gene name); lynD (gene name)
Systematic name: [protein]-(L-amino acyl-L-cysteine) cyclodehydratase (2-thiazoline-forming)
Comments: Requires Mg2+. The enzyme, which participates in the biosynthesis of some ribosomal peptide natural products (RiPPs) such as the trunkamides, converts L-cysteine residues to thiazoline rings. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple L-cysteine residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate. This activity is also catalysed by the related enzyme EC 6.2.2.2, oxazoline synthase. That enzyme differs by having an RRE domain that also recognizes L-serine and L-threonine residues, which are converted to oxazoline and methyloxazoline rings, respectively.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  McIntosh, J.A. and Schmidt, E.W. Marine molecular machines: heterocyclization in cyanobactin biosynthesis. ChemBioChem 11 (2010) 1413–1421. [PMID: 20540059]
2.  McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089–4091. [PMID: 20210311]
3.  Koehnke, J., Bent, A.F., Zollman, D., Smith, K., Houssen, W.E., Zhu, X., Mann, G., Lebl, T., Scharff, R., Shirran, S., Botting, C.H., Jaspars, M., Schwarz-Linek, U. and Naismith, J.H. The cyanobactin heterocyclase enzyme: a processive adenylase that operates with a defined order of reaction. Angew. Chem. Int. Ed. Engl. 52 (2013) 13991–13996. [PMID: 24214017]
4.  Koehnke, J., Mann, G., Bent, A.F., Ludewig, H., Shirran, S., Botting, C., Lebl, T., Houssen, W., Jaspars, M. and Naismith, J.H. Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat. Chem. Biol. 11 (2015) 558–563. [PMID: 26098679]
5.  Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125–2132. [PMID: 30912640]
[EC 6.2.2.3 created 2020]
 
 
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)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-69-2
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
For diagram of glutamic acid biosynthesis, click here
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.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9023-70-5
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. (Ed.), 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. [DOI] [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. [DOI] [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. [DOI] [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)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37318-61-9
References:
1.  Nair, P.M. Asparagine synthetase from γ-irradiated potatoes. Arch. Biochem. Biophys. 133 (1969) 208–215. [DOI] [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].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9032-69-3
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)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 62213-31-4
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 85537-85-5
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. [DOI] [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
For diagram of trypanothione biosynthesis, click here and for diagram of trypanothione biosynthesis, click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9077-09-2
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. [DOI] [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. [DOI] [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
For diagram of trypanothione biosynthesis, click here and for diagram of trypanothione biosynthesis, click here
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).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 130246-69-4
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. [DOI] [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. [DOI] [PMID: 12121990]
3.  Comini, M., Menge, U., Wissing, J. and Flohe, L. Trypanothione synthesis in crithidia revisited. J. Biol. Chem. 280 (2005) 6850–6860. [DOI] [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. [DOI] [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. [DOI] [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
For diagram of corrin biosynthesis (part 6), click here
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).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 905988-16-1
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. [DOI] [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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 914090-78-1
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. [DOI] [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
For diagram of reaction, click here
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]
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
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. [DOI] [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. [DOI] [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
For diagram of mycothiol biosynthesis, click here
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].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
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. [DOI] [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. [DOI] [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. [DOI] [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]
For diagram of diphthamide biosynthesis, click here
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 archaea and eukaryota, 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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 114514-33-9
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. [DOI] [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 + 4-hydroxy-3-prenylbenzoate + 3-amino-4,7-dihydroxycoumarin = AMP + diphosphate + 8-demethylnovobiocic acid
For diagram of novobiocin biosynthesis, click here
Glossary: 8-demethylnovobiocic acid = N-(2,7-dihydroxy-4-oxochromen-3-yl)-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide
Other name(s): novL (gene name); novobiocin ligase; novobiocic acid synthetase (misleading); 8-desmethyl-novobiocic acid synthetase; 8-demethylnovobiocic acid synthetase; 3-dimethylallyl-4-hydroxybenzoate:3-amino-4,7-dihydroxycoumarin ligase (AMP-forming)
Systematic name: 4-hydroxy-3-prenylbenzoate:3-amino-4,7-dihydroxycoumarin ligase (AMP-forming)
Comments: The enzyme is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
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. [DOI] [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. [DOI] [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. [DOI] [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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
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. [DOI] [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.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB
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. [DOI] [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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 144114-18-1
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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [PMID: 10966480]
[EC 6.3.1.20 created 2006 as EC 2.7.7.63, transferred 2016 to EC 6.3.1.20]
 
 
EC 6.3.1.21     
Accepted name: phosphoribosylglycinamide formyltransferase 2
Reaction: ATP + formate + N1-(5-phospho-β-D-ribosyl)glycinamide = ADP + phosphate + N2-formyl-N1-(5-phospho-β-D-ribosyl)glycinamide
Other name(s): purT (gene name); GAR transformylase 2; GART2; glycinamide ribonucleotide transformylase 2; 5′-phosphoribosylglycinamide transformylase 2; GAR transformylase T
Systematic name: formate:N1-(5-phospho-β-D-ribosyl)glycinamide ligase (ADP-forming)
Comments: Two enzymes are known to catalyse the third step in de novo purine biosynthesis. This enzyme requires ATP and utilizes formate, which is provided by the hydrolysis of 10-formyltetrahydrofolate by EC 3.5.1.10, formyltetrahydrofolate deformylase. The other enzyme, EC 2.1.2.2, phosphoribosylglycinamide formyltransferase 1, utilizes 10-formyltetrahydrofolate directly. Formyl phosphate is formed during catalysis as an intermediate. The enzyme from the bacterium Escherichia coli can also catalyse the activity of EC 2.7.2.1, acetate kinase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Nagy, P.L., McCorkle, G.M. and Zalkin, H. purU, a source of formate for purT-dependent phosphoribosyl-N-formylglycinamide synthesis. J. Bacteriol. 175 (1993) 7066–7073. [DOI] [PMID: 8226647]
2.  Nygaard, P. and Smith, J.M. Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli. J. Bacteriol. 175 (1993) 3591–3597. [DOI] [PMID: 8501063]
3.  Marolewski, A., Smith, J.M. and Benkovic, S.J. Cloning and characterization of a new purine biosynthetic enzyme: a non-folate glycinamide ribonucleotide transformylase from E. coli. Biochemistry 33 (1994) 2531–2537. [DOI] [PMID: 8117714]
4.  Marolewski, A.E., Mattia, K.M., Warren, M.S. and Benkovic, S.J. Formyl phosphate: a proposed intermediate in the reaction catalyzed by Escherichia coli PurT GAR transformylase. Biochemistry 36 (1997) 6709–6716. [DOI] [PMID: 9184151]
5.  Thoden, J.B., Firestine, S., Nixon, A., Benkovic, S.J. and Holden, H.M. Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide transformylase. Biochemistry 39 (2000) 8791–8802. [DOI] [PMID: 10913290]
6.  Jelsbak, L., Mortensen, M.IB., Kilstrup, M. and Olsen, J.E. The in vitro redundant enzymes PurN and PurT are both essential for systemic infection of mice in Salmonella enterica serovar Typhimurium. Infect. Immun. 84 (2016) 2076–2085. [DOI] [PMID: 27113361]
[EC 6.3.1.21 created 2021]
 
 
EC 6.3.2.1     
Accepted name: pantoate—β-alanine ligase (AMP-forming)
Reaction: ATP + (R)-pantoate + β-alanine = AMP + diphosphate + (R)-pantothenate
For diagram of coenzyme A biosynthesis (early stages), click here
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)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-49-8
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. [DOI] [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
For diagram of glutathione biosynthesis, click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-64-7
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. [DOI] [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
For diagram of glutathione biosynthesis, click here
Other name(s): glutathione synthetase; GSH synthetase
Systematic name: γ-L-glutamyl-L-cysteine:glycine ligase (ADP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-62-5
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).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-63-6
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
For diagram of coenzyme A biosynthesis (late stages), click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-50-1
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. [DOI] [PMID: 11278255]
3.  Kupke, T. Molecular characterization of the 4′-phosphopantothenoylcysteine synthetase domain of bacterial Dfp flavoproteins. J. Biol. Chem. 277 (2002) 36137–36145. [DOI] [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
For diagram of the late stages of purine biosynthesis, click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-67-0
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. [DOI] [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. [DOI] [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
For diagram of peptidoglycan biosynthesis (part 1), click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-51-2
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
For diagram of peptidoglycan biosynthesis (part 1), click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-52-3
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
For diagram of peptidoglycan biosynthesis (part 1), click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-59-0
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
For diagram of peptidoglycan biosynthesis (part 1), click here
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-2,6-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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 55354-36-4
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].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9023-61-4
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. [DOI] [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
For diagram of folate biosynthesis (late stages), click here
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 cofactor 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 responsible 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].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37318-62-0
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. [DOI] [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. [DOI] [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. [DOI] [PMID: 10799479]
5.  Cossins, E.A. and Chen, L. Folates and one-carbon metabolism in plants and fungi. Phytochemistry 45 (1997) 437–452. [DOI] [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
For diagram of peptidoglycan biosynthesis (part 1), click here
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9075-09-6
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
For diagram of enterobactin biosynthesis, click here
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).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37318-63-1
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. [DOI] [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. [DOI] [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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9046-58-6
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
For diagram of folate biosynthesis (late stages), click here
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 cofactor 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 cofactors 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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 63363-84-8
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. [DOI] [PMID: 6458762]
2.  McGuire, J.J. and Bertino, J.R. Enzymatic synthesis and function of folylpolyglutamates. Mol. Cell. Biochem. 38 (1981) 19–48. [DOI] [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. [DOI] [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. [DOI] [PMID: 11752472]
5.  Cossins, E.A. and Chen, L. Folates and one-carbon metabolism in plants and fungi. Phytochemistry 45 (1997) 437–452. [DOI] [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. [DOI] [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
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 82904-08-3
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. [DOI] [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]
 
 


Data © 2001–2024 IUBMB
Web site © 2005–2024 Andrew McDonald