EC |
1.1.1.205 |
Accepted name: |
IMP dehydrogenase |
Reaction: |
IMP + NAD+ + H2O = XMP + NADH + H+ |
|
For diagram of AMP and GMP biosynthesis, click here |
Glossary: |
IMP = inosine 5′-phosphate
XMP = xanthosine 5′-phosphate |
Other name(s): |
inosine-5′-phosphate dehydrogenase; inosinic acid dehydrogenase; inosinate dehydrogenase; inosine 5′-monophosphate dehydrogenase; inosine monophosphate dehydrogenase; IMP oxidoreductase; inosine monophosphate oxidoreductase |
Systematic name: |
IMP:NAD+ oxidoreductase |
Comments: |
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-93-7 |
References: |
1. |
Magasanik, B., Moyed, H.S. and Gehring, L.B. Enzymes essential for the biosynthesis of nucleic acid guanine; inosine 5′-phosphate dehydrogenase of Aerobacter aerogenes. J. Biol. Chem. 226 (1957) 339–350. [PMID: 13428767] |
2. |
Turner, J.F. and King, J.E. Inosine 5-phosphate dehydrogenase of pea seeds. Biochem. J. 79 (1961) 147. [PMID: 13778733] |
|
[EC 1.1.1.205 created 1961 as EC 1.2.1.14, transferred 1984 to EC 1.1.1.205] |
|
|
|
|
EC
|
1.6.6.8
|
Transferred entry: | GMP reductase. Now EC 1.7.1.7, GMP reductase
|
[EC 1.6.6.8 created 1965, deleted 2002] |
|
|
|
|
EC |
1.7.1.7 |
Accepted name: |
GMP reductase |
Reaction: |
IMP + NH3 + NADP+ = GMP + NADPH + H+ |
Glossary: |
IMP = inosine 5′-phosphate
GMP = guanosine 5′-phosphate |
Other name(s): |
guanosine 5′-monophosphate reductase; NADPH:GMP oxidoreductase (deaminating); guanosine monophosphate reductase; guanylate reductase; NADPH2:guanosine-5′-phosphate oxidoreductase (deaminating); guanosine 5′-phosphate reductase |
Systematic name: |
inosine-5′-phosphate:NADP+ oxidoreductase (aminating) |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-32-7 |
References: |
1. |
MacKenzie, J.J. and Sorensen, L.B. Guanosine 5′-phosphate reductase of human erythrocytes. Biochim. Biophys. Acta 327 (1973) 282–294. [DOI] [PMID: 4149840] |
2. |
Mager, J. and Magasanik, B. Guanosine 5′-phosphate reductase and its role in the interconversion of purine nucleotides. J. Biol. Chem. 235 (1960) 1474–1478. [PMID: 14419794] |
|
[EC 1.7.1.7 created 1965 as EC 1.6.6.8, transferred 2002 to EC 1.7.1.7] |
|
|
|
|
EC |
2.4.2.8 |
Accepted name: |
hypoxanthine phosphoribosyltransferase |
Reaction: |
IMP + diphosphate = hypoxanthine + 5-phospho-α-D-ribose 1-diphosphate |
Other name(s): |
IMP pyrophosphorylase; transphosphoribosidase; hypoxanthine—guanine phosphoribosyltransferase; guanine phosphoribosyltransferase; GPRT; HPRT; guanosine 5′-phosphate pyrophosphorylase; IMP-GMP pyrophosphorylase; HGPRTase; 6-hydroxypurine phosphoribosyltransferase; 6-mercaptopurine phosphoribosyltransferase; GMP pyrophosphorylase; guanine-hypoxanthine phosphoribosyltransferase; guanosine phosphoribosyltransferase; guanylate pyrophosphorylase; guanylic pyrophosphorylase; inosinate pyrophosphorylase; inosine 5′-phosphate pyrophosphorylase; inosinic acid pyrophosphorylase; inosinic pyrophosphorylase; purine-6-thiol phosphoribosyltransferase |
Systematic name: |
IMP:diphosphate phospho-D-ribosyltransferase |
Comments: |
Guanine and purine-6-thiol can replace hypoxanthine. |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9016-12-0 |
References: |
1. |
Flaks, J.G. Nucleotide synthesis from 5-phosphoribosylpyrophosphate. Methods Enzymol. 6 (1963) 136–158. |
2. |
Kornberg, A., Lieberman, I. and Simms, E.S. Enzymatic synthesis of purine nucleotides. J. Biol. Chem. 215 (1955) 417–427. [PMID: 14392175] |
3. |
Lukens, L.N. and Herrington, K.A. Enzymic formation of 6-mercaptopurine ribotide. Biochim. Biophys. Acta 24 (1957) 432–433. [PMID: 13436452] |
4. |
Remy, C.N., Remy, W.T. and Buchanan, J.M. Biosynthesis of the purines. VIII. Enzymatic synthesis and utilization of α-5-phosphoribosylpyrophosphate. J. Biol. Chem. 217 (1955) 885–895. [PMID: 13271449] |
|
[EC 2.4.2.8 created 1961, modified 1982] |
|
|
|
|
EC |
2.4.99.16 |
Accepted name: |
starch synthase (maltosyl-transferring) |
Reaction: |
α-maltose 1-phosphate + [(1→4)-α-D-glucosyl]n = phosphate + [(1→4)-α-D-glucosyl]n+2 |
Other name(s): |
α1,4-glucan:maltose-1-P maltosyltransferase; GMPMT |
Systematic name: |
α-maltose 1-phosphate:(1→4)-α-D-glucan 4-α-D-maltosyltransferase |
Comments: |
The enzyme from the bacterium Mycobacterium smegmatis is specific for maltose. It has no activity with α-D-glucose. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Elbein, A.D., Pastuszak, I., Tackett, A.J., Wilson, T. and Pan, Y.T. Last step in the conversion of trehalose to glycogen: a mycobacterial enzyme that transfers maltose from maltose 1-phosphate to glycogen. J. Biol. Chem. 285 (2010) 9803–9812. [DOI] [PMID: 20118231] |
2. |
Syson, K., Stevenson, C.E., Rejzek, M., Fairhurst, S.A., Nair, A., Bruton, C.J., Field, R.A., Chater, K.F., Lawson, D.M. and Bornemann, S. Structure of Streptomyces maltosyltransferase GlgE, a homologue of a genetically validated anti-tuberculosis target. J. Biol. Chem. 286 (2011) 38298–38310. [DOI] [PMID: 21914799] |
|
[EC 2.4.99.16 created 2012] |
|
|
|
|
EC
|
2.7.1.37
|
Transferred entry: | protein kinase. Now divided into EC 2.7.11.1 (non-specific serine/threonine protein kinase), EC 2.7.11.8 (Fas-activated serine/threonine kinase), EC 2.7.11.9 (Goodpasture-antigen-binding protein kinase), EC 2.7.11.10 (IκB kinase), EC 2.7.11.11 (cAMP-dependent protein kinase), EC 2.7.11.12 (cGMP-dependent protein kinase), EC 2.7.11.13 (protein kinase C), EC 2.7.11.21 (polo kinase), EC 2.7.11.22 (cyclin-dependent kinase), EC 2.7.11.24 (mitogen-activated protein kinase), EC 2.7.11.25 (mitogen-activated protein kinase kinase kinase), EC 2.7.11.30 (receptor protein serine/threonine kinase) and EC 2.7.12.1 (dual-specificity kinase)
|
[EC 2.7.1.37 created 1961 (EC 2.7.1.70 incorporated 2004), deleted 2005] |
|
|
|
|
EC |
2.7.1.113 |
Accepted name: |
deoxyguanosine kinase |
Reaction: |
ATP + deoxyguanosine = ADP + dGMP |
Other name(s): |
deoxyguanosine kinase (phosphorylating); (dihydroxypropoxymethyl)guanine kinase; 2′-deoxyguanosine kinase; NTP-deoxyguanosine 5′-phosphotransferase |
Systematic name: |
ATP:deoxyguanosine 5′-phosphotransferase |
Comments: |
Deoxyinosine can also act as acceptor. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 39471-28-8 |
References: |
1. |
Barker, J. and Lewis, R.A. Deoxyguanosine kinase of neonatal mouse skin tissue. Biochim. Biophys. Acta 658 (1981) 111–123. [DOI] [PMID: 6260206] |
2. |
Gower, W.R., Jr., Carr, M.C. and Ives, D.H. Deoxyguanosine kinase. Distinct molecular forms in mitochondria and cytosol. J. Biol. Chem. 254 (1979) 2180–2183. [PMID: 218928] |
|
[EC 2.7.1.113 created 1984] |
|
|
|
|
EC |
2.7.1.143 |
Accepted name: |
diphosphate-purine nucleoside kinase |
Reaction: |
diphosphate + a purine nucleoside = phosphate + a purine mononucleotide |
Other name(s): |
pyrophosphate-purine nucleoside kinase |
Systematic name: |
diphosphate:purine nucleoside phosphotransferase |
Comments: |
The enzyme from the Acholeplasma class of Mollicutes catalyses the conversion of adenosine, guanosine and inosine to AMP, GMP and IMP. ATP cannot substitute for diphosphate as a substrate. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 70356-41-1 |
References: |
1. |
Tryon, V.V., Pollack, D. Purine metabolism in Acholeplasma laidlawii B: novel PPi-dependent nucleoside kinase activity. J. Bacteriol. 159 (1984) 265–270. [PMID: 6330034] |
2. |
Tryon, V.V., Pollack, J.D. Distinctions in Mollicutes purine metabolism: pyrophosphate-dependent nucleoside kinase and dependence on guanylate salvage. Int. J. Systematic Bacteriol. 35 (1985) 497–501. |
|
[EC 2.7.1.143 created 1999] |
|
|
|
|
EC |
2.7.1.156 |
Accepted name: |
adenosylcobinamide kinase |
Reaction: |
RTP + adenosylcobinamide = adenosylcobinamide phosphate + RDP [where RTP is either ATP or GTP (for symbol definitions, click here)] |
|
For diagram of the enzyme’s role in corrin biosynthesis, click here |
Other name(s): |
CobU; adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase; AdoCbi kinase/AdoCbi-phosphate guanylyltransferase |
Systematic name: |
RTP:adenosylcobinamide phosphotransferase |
Comments: |
In Salmonella typhimurium LT2, under anaerobic conditions, CobU (EC 2.7.7.62 and EC 2.7.1.156), CobT (EC 2.4.2.21), CobC (EC 3.1.3.73) and CobS (EC 2.7.8.26) catalyse reactions in the nucleotide loop assembly pathway, which convert adenosylcobinamide (AdoCbi) into adenosylcobalamin (AdoCbl). CobT and CobC are involved in 5,6-dimethylbenzimidazole activation whereby 5,6-dimethylbenzimidazole is converted to its riboside, α-ribazole. The second branch of the nucleotide loop assembly pathway is the cobinamide (Cbi) activation branch where AdoCbi or adenosylcobinamide-phosphate is converted to the activated intermediate AdoCbi-GDP by Cob U. The final step in adenosylcobalamin biosynthesis is the condensation of AdoCbi-GDP with α-ribazole, which is catalysed by EC 2.7.8.26, adenosylcobinamide-GDP ribazoletransferase (CobS), to yield adenosylcobalamin. CobU is a bifunctional enzyme that has both kinase (EC 2.7.1.156) and guanylyltransferase (EC 2.7.7.62, adenosylcobinamide-phosphate guanylyltransferase) activities. However, both activities are not required at all times. The kinase activity has been proposed to function only when S. typhimurium is assimilating cobinamide whereas the guanylyltransferase activity is required for both assimilation of exogenous cobinamide and for de novo synthesis of adenosylcobalamin [4]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 169592-51-2 |
References: |
1. |
O'Toole, G.A. and Escalante-Semerena, J.C. Purification and characterization of the bifunctional CobU enzyme of Salmonella typhimurium LT2. Evidence for a CobU-GMP intermediate. J. Biol. Chem. 270 (1995) 23560–23569. [DOI] [PMID: 7559521] |
2. |
Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 Å resolution. Biochemistry 37 (1998) 7686–7695. [DOI] [PMID: 9601028] |
3. |
Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase (CobU) complexed with GMP: evidence for a substrate-induced transferase active site. Biochemistry 38 (1999) 12995–13005. [DOI] [PMID: 10529169] |
4. |
Thomas, M.G., Thompson, T.B., Rayment, I. and Escalante-Semerena, J.C. Analysis of the adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase (CobU) enzyme of Salmonella typhimurium LT2. Identification of residue His-46 as the site of guanylylation. J. Biol. Chem. 275 (2000) 27576–27586. [DOI] [PMID: 10869342] |
5. |
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 2.7.1.156 created 2004] |
|
|
|
|
EC |
2.7.4.8 |
Accepted name: |
guanylate kinase |
Reaction: |
ATP + GMP = ADP + GDP |
|
For diagram of GTP biosynthesis, click here |
Other name(s): |
deoxyguanylate kinase; 5′-GMP kinase; GMP kinase; guanosine monophosphate kinase; ATP:GMP phosphotransferase |
Systematic name: |
ATP:(d)GMP phosphotransferase |
Comments: |
dGMP can also act as acceptor, and dATP can act as donor. |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9026-59-9 |
References: |
1. |
Buccino, R.J., Jr. and Roth, J.S. Partial purification and properties of ATP:GMP phosphotransferase from rat liver. Arch. Biochem. Biophys. 132 (1969) 49–61. [DOI] [PMID: 4307347] |
2. |
Hiraga, S. and Sugino, Y. Nucleoside monophosphokinases of Escherichia coli infected and uninfected with an RNA phage. Biochim. Biophys. Acta 114 (1966) 416–418. [DOI] [PMID: 5329274] |
3. |
Griffith, T.J. and Helleiner, C.W. The partial purification of deoxynucleoside monophosphate kinases from L cells. Biochim. Biophys. Acta 108 (1965) 114–124. [DOI] [PMID: 5862227] |
4. |
Oeschger, M.P. and Bessman, M.J. Purification and properties of guanylate kinase from Escherichia coli. J. Biol. Chem. 241 (1966) 5452–5460. [PMID: 5333666] |
5. |
Shimono, H. and Sugino, Y. Metabolism of deoxyribonucleotides. Purification and properties of deoxyguanosine monophosphokinase of calf thymus. Eur. J. Biochem. 19 (1971) 256–263. [DOI] [PMID: 5552394] |
|
[EC 2.7.4.8 created 1965] |
|
|
|
|
EC |
2.7.4.12 |
Accepted name: |
T2-induced deoxynucleotide kinase |
Reaction: |
ATP + dGMP (or dTMP) = ADP + dGDP (or dTDP) |
Systematic name: |
ATP:(d)NMP phosphotransferase |
Comments: |
dTMP and dAMP can act as acceptors; dATP can act as donor. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37278-99-2 |
References: |
1. |
Bello, L.J. and Bessman, M.J. The enzymology of virus-infected bacteria. IV. Purification and properties of the deoxynucleotide kinase induced by bacteriophage T2. J. Biol. Chem. 238 (1963) 1777–1787. [PMID: 13967158] |
|
[EC 2.7.4.12 created 1972] |
|
|
|
|
EC |
2.7.4.33 |
Accepted name: |
AMP-polyphosphate phosphotransferase |
Reaction: |
ADP + (phosphate)n = AMP + (phosphate)n+1 |
Other name(s): |
PA3455 (locus name); PPK2D; PAP |
Systematic name: |
ADP:polyphosphate phosphotransferase |
Comments: |
The enzyme, characterized from the bacteria Acinetobacter johnsonii and Pseudomonas aeruginosa, transfers a phosphate group from polyphosphates to nucleotide monophosphates. The highest activity is achieved with AMP, but the enzyme can also phosphorylate GMP, dAMP, dGMP, IMP, and XMP. The reverse reactions were not detected. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Bonting, C.F., Kortstee, G.J. and Zehnder, A.J. Properties of polyphosphate: AMP phosphotransferase of Acinetobacter strain 210A. J. Bacteriol. 173 (1991) 6484–6488. [PMID: 1655714] |
2. |
Shiba, T., Itoh, H., Kameda, A., Kobayashi, K., Kawazoe, Y. and Noguchi, T. Polyphosphate:AMP phosphotransferase as a polyphosphate-dependent nucleoside monophosphate kinase in Acinetobacter johnsonii 210A. J. Bacteriol. 187 (2005) 1859–1865. [PMID: 15716459] |
3. |
Nocek, B., Kochinyan, S., Proudfoot, M., Brown, G., Evdokimova, E., Osipiuk, J., Edwards, A.M., Savchenko, A., Joachimiak, A. and Yakunin, A.F. Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria. Proc. Natl. Acad. Sci. USA 105 (2008) 17730–17735. [PMID: 19001261] |
|
[EC 2.7.4.33 created 2020] |
|
|
|
|
EC |
2.7.7.13 |
Accepted name: |
mannose-1-phosphate guanylyltransferase |
Reaction: |
GTP + α-D-mannose 1-phosphate = diphosphate + GDP-mannose |
|
For diagram of GDP-L-fucose and GDP-mannose biosynthesis, click here |
Other name(s): |
GTP-mannose-1-phosphate guanylyltransferase; PIM-GMP (phosphomannose isomerase-guanosine 5′-diphospho-D-mannose pyrophosphorylase); GDP-mannose pyrophosphorylase; guanosine 5′-diphospho-D-mannose pyrophosphorylase; guanosine diphosphomannose pyrophosphorylase; guanosine triphosphate-mannose 1-phosphate guanylyltransferase; mannose 1-phosphate guanylyltransferase (guanosine triphosphate) |
Systematic name: |
GTP:α-D-mannose-1-phosphate guanylyltransferase |
Comments: |
The bacterial enzyme can also use ITP and dGTP as donors. |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 37278-24-3 |
References: |
1. |
Munch-Peterson, A. Enzymatic synthesis and phosphorolysis of guanosine diphosphate mannose. Arch. Biochem. Biophys. 55 (1955) 592–593. |
2. |
Preiss, J. and Wood, E. Sugar nucleotide reactions in Arthrobacter. I. Guanosinediphosphate mannose pyrophosphorylase: purification and properties. J. Biol. Chem. 239 (1964) 3119–3126. [PMID: 14245350] |
|
[EC 2.7.7.13 created 1961, modified 1976] |
|
|
|
|
EC |
2.7.7.62 |
Accepted name: |
adenosylcobinamide-phosphate guanylyltransferase |
Reaction: |
GTP + adenosylcobinamide phosphate = diphosphate + adenosylcobinamide-GDP |
|
For diagram of the enzyme’s role in corrin biosynthesis, click here |
Other name(s): |
CobU; adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase; AdoCbi kinase/AdoCbi-phosphate guanylyltransferase |
Systematic name: |
GTP:adenosylcobinamide-phosphate guanylyltransferase |
Comments: |
In Salmonella typhimurium LT2, under anaerobic conditions, CobU (EC 2.7.7.62 and EC 2.7.1.156), CobT (EC 2.4.2.21), CobC (EC 3.1.3.73) and CobS (EC 2.7.8.26) catalyse reactions in the nucleotide loop assembly pathway, which convert adenosylcobinamide (AdoCbi) into adenosylcobalamin (AdoCbl). CobT and CobC are involved in 5,6-dimethylbenzimidazole activation whereby 5,6-dimethylbenzimidazole is converted to its riboside, α-ribazole. The second branch of the nuclotide loop assembly pathway is the cobinamide (Cbi) activation branch where AdoCbi or adenosylcobinamide-phosphate is converted to the activated intermediate AdoCbi-GDP by the bifunctional enzyme Cob U. The final step in adenosylcobalamin biosynthesis is the condensation of AdoCbi-GDP with α-ribazole, which is catalysed by EC 2.7.8.26, cobalamin synthase (CobS), to yield adenosylcobalamin. CobU is a bifunctional enzyme that has both kinase (EC 2.7.1.156) and guanylyltransferase (EC 2.7.7.62) activities. However, both activities are not required at all times.The kinase activity has been proposed to function only when S. typhimurium is assimilating cobinamide whereas the guanylyltransferase activity is required for both assimilation of exogenous cobinamide and for de novo synthesis of adenosylcobalamin [4]. The guanylyltransferase reaction is a two-stage reaction with formation of a CobU-GMP intermediate [1]. Guanylylation takes place at histidine-46. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 169592-55-6 |
References: |
1. |
O'Toole, G.A. and Escalante-Semerena, J.C. Purification and characterization of the bifunctional CobU enzyme of Salmonella typhimurium LT2. Evidence for a CobU-GMP intermediate. J. Biol. Chem. 270 (1995) 23560–23569. [DOI] [PMID: 7559521] |
2. |
Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 Å resolution. Biochemistry 37 (1998) 7686–7695. [DOI] [PMID: 9601028] |
3. |
Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C. and Rayment, I. Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase (CobU) complexed with GMP: evidence for a substrate-induced transferase active site. Biochemistry 38 (1999) 12995–13005. [DOI] [PMID: 10529169] |
4. |
Thomas, M.G., Thompson, T.B., Rayment, I. and Escalante-Semerena, J.C. Analysis of the adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase (CobU) enzyme of Salmonella typhimurium LT2. Identification of residue His-46 as the site of guanylylation. J. Biol. Chem. 275 (2000) 27576–27586. [DOI] [PMID: 10869342] |
5. |
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 2.7.7.62 created 2004] |
|
|
|
|
EC |
2.7.7.65 |
Accepted name: |
diguanylate cyclase |
Reaction: |
2 GTP = 2 diphosphate + cyclic di-3′,5′-guanylate |
|
For diagram of cyclic di-3′,5′-guanylate biosynthesis and breakdown, click here |
Glossary: |
cyclic di-3′,5′-guanylate = c-di-GMP = c-di-guanylate = cyclic-bis(3′→5′) dimeric GMP |
Other name(s): |
DGC; PleD |
Systematic name: |
GTP:GTP guanylyltransferase (cyclizing) |
Comments: |
A GGDEF-domain-containing protein that requires Mg2+ or Mn2+ for activity. The enzyme can be activated by BeF3, a phosphoryl mimic, which results in dimerization [3]. Dimerization is required but is not sufficient for diguanylate-cyclase activity [3]. Cyclic di-3′,5′-guanylate is an intracellular signalling molecule that controls motility and adhesion in bacterial cells. It was first identified as having a positive allosteric effect on EC 2.4.1.12, cellulose synthase (UDP-forming) [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 146316-82-7 |
References: |
1. |
Ryjenkov, D.A., Tarutina, M., Moskvin, O.V. and Gomelsky, M. Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into biochemistry of the GGDEF protein domain. J. Bacteriol. 187 (2005) 1792–1798. [DOI] [PMID: 15716451] |
2. |
Méndez-Ortiz, M.M., Hyodo, M., Hayakawa, Y. and Membrillo-Hernández, J. Genome-wide transcriptional profile of Escherichia coli in response to high levels of the second messenger 3′,5′-cyclic diguanylic acid. J. Biol. Chem. 281 (2006) 8090–8099. [DOI] [PMID: 16418169] |
3. |
Paul, R., Abel, S., Wassmann, P., Beck, A., Heerklotz, H. and Jenal, U. Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization. J. Biol. Chem. 282 (2007) 29170–29177. [DOI] [PMID: 17640875] |
|
[EC 2.7.7.65 created 2008] |
|
|
|
|
EC |
2.7.7.86 |
Accepted name: |
cyclic GMP-AMP synthase |
Reaction: |
ATP + GTP = 2 diphosphate + cyclic Gp(2′-5′)Ap(3′-5′) (overall reaction) (1a) ATP + GTP = pppGp(2′-5′)A + diphosphate (1b) pppGp(2′-5′)A = cyclic Gp(2′-5′)Ap(3′-5′) + diphosphate |
Glossary: |
cyclic Gp(2′-5′)Ap(3′-5′) = cyclo[(3′→5′)-guanylyl-(2′→5′)-adenylyl] |
Other name(s): |
cGAMP synthase; cGAS |
Systematic name: |
ATP:GTP adenylyltransferase (cyclizing) |
Comments: |
Cyclic Gp(2′-5′)Ap(3′-5′) is a signalling molecule in mammalian cells that triggers the production of type I interferons and other cytokines. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Sun, L., Wu, J., Du, F., Chen, X. and Chen, Z.J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339 (2013) 786–791. [DOI] [PMID: 23258413] |
2. |
Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Rohl, I., Hopfner, K.P., Ludwig, J. and Hornung, V. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 498 (2013) 380–384. [DOI] [PMID: 23722158] |
|
[EC 2.7.7.86 created 2013, modified 2014] |
|
|
|
|
EC |
2.7.8.9 |
Accepted name: |
phosphomannan mannosephosphotransferase |
Reaction: |
GDP-mannose + (phosphomannan)n = GMP + (phosphomannan)n+1 |
Systematic name: |
GDP-mannose:phosphomannan mannose phosphotransferase |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37278-31-2 |
References: |
1. |
Bretthauer, R.K., Kozak, L.P. and Irwin, W.E. Phosphate and mannose transfer from guanosine diphosphate mannose to yeast mannan acceptors. Biochem. Biophys. Res. Commun. 37 (1969) 820–827. [DOI] [PMID: 4311996] |
|
[EC 2.7.8.9 created 1972] |
|
|
|
|
EC |
2.7.8.26 |
Accepted name: |
adenosylcobinamide-GDP ribazoletransferase |
Reaction: |
(1) adenosylcobinamide-GDP + α-ribazole = GMP + adenosylcobalamin (2) adenosylcobinamide-GDP + α-ribazole 5′-phosphate = GMP + adenosylcobalamin 5′-phosphate |
|
For diagram of the enzyme's role in corrin biosynthesis, click here |
Other name(s): |
CobS; cobalamin synthase; cobalamin-5′-phosphate synthase; cobalamin (5′-phosphate) synthase |
Systematic name: |
adenosylcobinamide-GDP:α-ribazole ribazoletransferase |
Comments: |
In Salmonella typhimurium LT2, under anaerobic conditions, CobU (EC 2.7.7.62 and EC 2.7.1.156), CobT (EC 2.4.2.21), CobC (EC 3.1.3.73) and CobS (EC 2.7.8.26) catalyse reactions in the nucleotide loop assembly pathway, which convert adenosylcobinamide (AdoCbi) into adenosylcobalamin (AdoCbl). CobT and CobC are involved in 5,6-dimethylbenzimidazole activation whereby 5,6-dimethylbenzimidazole is converted to its riboside, α-ribazole. The second branch of the nucleotide loop assembly pathway is the cobinamide activation branch where AdoCbi or adenosylcobinamide-phosphate is converted to the activated intermediate AdoCbi-GDP by the bifunctional enzyme Cob U. CobS catalyses the final step in adenosylcobalamin biosynthesis, which is the condensation of AdoCbi-GDP with α-ribazole to yield adenosylcobalamin. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 137672-85-6 |
References: |
1. |
Maggio-Hall, L.A. and Escalante-Semerena, J.C. In vitro synthesis of the nucleotide loop of cobalamin by Salmonella typhimurium enzymes. Proc. Natl. Acad. Sci. USA 96 (1999) 11798–11803. [DOI] [PMID: 10518530] |
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] |
3. |
Cameron, B., Blanche, F., Rouyez, M.C., Bisch, D., Famechon, A., Couder, M., Cauchois, L., Thibaut, D., Debussche, L. and Crouzet, J. Genetic analysis, nucleotide sequence, and products of two Pseudomonas denitrificans cob genes encoding nicotinate-nucleotide: dimethylbenzimidazole phosphoribosyltransferase and cobalamin (5′-phosphate) synthase. J. Bacteriol. 173 (1991) 6066–6073. [DOI] [PMID: 1917841] |
|
[EC 2.7.8.26 created 2004] |
|
|
|
|
EC |
2.7.8.28 |
Accepted name: |
2-phospho-L-lactate transferase |
Reaction: |
(1) (2S)-lactyl-2-diphospho-5′-guanosine + 7,8-didemethyl-8-hydroxy-5-deazariboflavin = GMP + factor 420-0 (2) enolpyruvoyl-2-diphospho-5′-guanosine + 7,8-didemethyl-8-hydroxy-5-deazariboflavin = GMP + dehydro factor 420-0 (3) 3-[(R)-glyceryl]-diphospho-5′-guanosine + 7,8-didemethyl-8-hydroxy-5-deazariboflavin = GMP + 3PG-factor 420-0 |
|
For diagram of coenzyme F420 biosynthesis, click here |
Glossary: |
factor 420 = 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
dehydro coenzyme F420-0 = 7,8-didemethyl-8-hydroxy-5-deazariboflavin 5′-(1-carboxyvinyl)phosphate
GMP = guanosine 5′-phosphate |
Other name(s): |
cofD (gene name); fbiA (gene name); LPPG:Fo 2-phospho-L-lactate transferase; LPPG:7,8-didemethyl-8-hydroxy-5-deazariboflavin 2-phospho-L-lactate transferase; lactyl-2-diphospho-(5′)guanosine:Fo 2-phospho-L-lactate transferase |
Systematic name: |
(2S)-lactyl-2-diphospho-5′-guanosine:7,8-didemethyl-8-hydroxy-5-deazariboflavin 2-phospho-L-lactate transferase |
Comments: |
This enzyme is involved in the biosynthesis of factor 420, a redox-active cofactor, in methanogenic archaea and certain bacteria. The specific reaction catalysed in vivo is determined by the availability of substrate, which in turn is determined by the enzyme present in the organism - EC 2.7.7.68, 2-phospho-L-lactate guanylyltransferase, EC 2.7.7.105, phosphoenolpyruvate guanylyltransferase, or EC 2.7.7.106, 3-phospho-D-glycerate guanylyltransferase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Graupner, M., Xu, H. and White, R.H. Characterization of the 2-phospho-L-lactate transferase enzyme involved in coenzyme F420 biosynthesis in Methanococcus jannaschii. Biochemistry 41 (2002) 3754–3761. [DOI] [PMID: 11888293] |
2. |
Forouhar, F., Abashidze, M., Xu, H., Grochowski, L.L., Seetharaman, J., Hussain, M., Kuzin, A., Chen, Y., Zhou, W., Xiao, R., Acton, T.B., Montelione, G.T., Galinier, A., White, R.H. and Tong, L. Molecular insights into the biosynthesis of the F420 coenzyme. J. Biol. Chem. 283 (2008) 11832–11840. [DOI] [PMID: 18252724] |
3. |
Braga, D., Last, D., Hasan, M., Guo, H., Leichnitz, D., Uzum, Z., Richter, I., Schalk, F., Beemelmanns, C., Hertweck, C. and Lackner, G. Metabolic pathway rerouting in Paraburkholderia rhizoxinica evolved long-overlooked derivatives of coenzyme F420. ACS Chem. Biol. 14 (2019) 2088–2094. [PMID: 31469543] |
|
[EC 2.7.8.28 created 2010, modified 2020] |
|
|
|
|
EC |
2.7.11.1 |
Accepted name: |
non-specific serine/threonine protein kinase |
Reaction: |
ATP + a protein = ADP + a phosphoprotein |
Other name(s): |
A-kinase; AP50 kinase; ATP-protein transphosphorylase; calcium-dependent protein kinase C; calcium/phospholipid-dependent protein kinase; cAMP-dependent protein kinase; cAMP-dependent protein kinase A; casein kinase; casein kinase (phosphorylating); casein kinase 2; casein kinase I; casein kinase II; cGMP-dependent protein kinase; CK-2; CKI; CKII; cyclic AMP-dependent protein kinase; cyclic AMP-dependent protein kinase A; cyclic monophosphate-dependent protein kinase; cyclic nucleotide-dependent protein kinase; cyclin-dependent kinase; cytidine 3′,5′-cyclic monophosphate-responsive protein kinase; dsk1; glycogen synthase a kinase; glycogen synthase kinase; HIPK2; Hpr kinase; hydroxyalkyl-protein kinase; hydroxyalkyl-protein kinase; M phase-specific cdc2 kinase; mitogen-activated S6 kinase; p82 kinase; phosphorylase b kinase kinase; PKA; protein glutamyl kinase; protein kinase (phosphorylating); protein kinase A; protein kinase CK2; protein kinase p58; protein phosphokinase; protein serine kinase; protein serine-threonine kinase; protein-aspartyl kinase; protein-cysteine kinase; protein-serine kinase; Prp4 protein kinase; Raf kinase; Raf-1; ribosomal protein S6 kinase II; ribosomal S6 protein kinase; serine kinase; serine protein kinase; serine-specific protein kinase; serine(threonine) protein kinase; serine/threonine protein kinase; STK32; T-antigen kinase; threonine-specific protein kinase; twitchin kinase; type-2 casein kinase; βIIPKC; ε PKC; Wee 1-like kinase; Wee-kinase; WEE1Hu |
Systematic name: |
ATP:protein phosphotransferase (non-specific) |
Comments: |
This is a heterogeneous group of serine/threonine protein kinases that do not have an activating compound and are either non-specific or their specificity has not been analysed to date. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Damuni, Z. and Reed, L.J. Purification and properties of a protamine kinase and a type II casein kinase from bovine kidney mitochondria. Arch. Biochem. Biophys. 262 (1988) 574–584. [DOI] [PMID: 2835010] |
2. |
Baggio, B., Pinna, L.A., Moret, V. and Siliprandi, N. A simple procedure for the purification of rat liver phosvitin kinase. Biochim. Biophys. Acta 212 (1970) 515–517. [DOI] [PMID: 5456997] |
3. |
Jergil, B. and Dixon, G.H. Protamine kinase from rainbow trout testis. Partial purification and characterization. J. Biol. Chem. 245 (1970) 425–434. [PMID: 4312674] |
4. |
Langan, T.A. Action of adenosine 3′,5′-monophosphate-dependent histone kinase in vivo. J. Biol. Chem. 244 (1969) 5763–5765. [PMID: 4310608] |
5. |
Takeuchi, M. and Yanagida, M. A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization. Mol. Biol. Cell 4 (1993) 247–260. [DOI] [PMID: 8485317] |
6. |
Gross, T., Lutzelberger, M., Weigmann, H., Klingenhoff, A., Shenoy, S. and Kaufer, N.F. Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue. Nucleic Acids Res. 25 (1997) 1028–1035. [DOI] [PMID: 9102632] |
7. |
Wang, Y., Hofmann, T.G., Runkel, L., Haaf, T., Schaller, H., Debatin, K. and Hug, H. Isolation and characterization of cDNAs for the protein kinase HIPK2. Biochim. Biophys. Acta 1518 (2001) 168–172. [DOI] [PMID: 11267674] |
|
[EC 2.7.11.1 created 2005 (EC 2.7.1.37 part-incorporated 2005] |
|
|
|
|
EC |
2.7.11.12 |
Accepted name: |
cGMP-dependent protein kinase |
Reaction: |
ATP + a protein = ADP + a phosphoprotein |
Other name(s): |
3′:5′-cyclic GMP-dependent protein kinase; cGMP-dependent protein kinase Iβ; guanosine 3′:5′-cyclic monophosphate-dependent protein kinase; PKG; PKG 1α; PKG 1β; PKG II; STK23 |
Systematic name: |
ATP:protein phosphotransferase (cGMP-dependent) |
Comments: |
CGMP is required to activate this enzyme. The enzyme occurs as a dimer in higher eukaryotes. The C-terminal region of each polypeptide chain contains the catalytic domain that includes the ATP and protein substrate binding sites. This domain catalyses the phosphorylation by ATP to specific serine or threonine residues in protein substrates [3]. The enzyme also has two allosteric cGMP-binding sites (sites A and B). Binding of cGMP causes a conformational change that is associated with activation of the kinase [4]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 141588-27-4 |
References: |
1. |
Gill, G.N., Holdy, K.E., Walton, G.M. and Kanstein, C.B. Purification and characterization of 3′:5′-cyclic GMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA 73 (1976) 3918–3922. [DOI] [PMID: 186778] |
2. |
Murthy, K.S. Modulation of soluble guanylate cyclase activity by phosphorylation. Neurochem. Int. 45 (2004) 845–851. [DOI] [PMID: 15312978] |
3. |
Richie-Jannetta, R., Francis, S.H. and Corbin, J.D. Dimerization of cGMP-dependent protein kinase Iβ is mediated by an extensive amino-terminal leucine zipper motif, and dimerization modulates enzyme function. J. Biol. Chem. 278 (2003) 50070–50079. [DOI] [PMID: 12933804] |
4. |
Zhao, J., Trewhella, J., Corbin, J., Francis, S., Mitchell, R., Brushia, R. and Walsh, D. Progressive cyclic nucleotide-induced conformational changes in the cGMP-dependent protein kinase studied by small angle X-ray scattering in solution. J. Biol. Chem. 272 (1997) 31929–31936. [DOI] [PMID: 9395542] |
|
[EC 2.7.11.12 created 2005 (EC 2.7.1.37 part-incorporated 2005)] |
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|
|
|
EC |
3.1.3.91 |
Accepted name: |
7-methylguanosine nucleotidase |
Reaction: |
(1) N7-methyl-GMP + H2O = N7-methyl-guanosine + phosphate (2) CMP + H2O = cytidine + phosphate |
Other name(s): |
cytosolic nucleotidase III-like; cNIII-like; N7-methylguanylate 5′-phosphatase |
Systematic name: |
N7-methyl-GMP phosphohydrolase |
Comments: |
The enzyme also has low activity with N7-methyl-GDP, producing N7-methyl-GMP. Does not accept AMP or GMP, and has low activity with UMP. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Buschmann, J., Moritz, B., Jeske, M., Lilie, H., Schierhorn, A. and Wahle, E. Identification of Drosophila and human 7-methyl GMP-specific nucleotidases. J. Biol. Chem. 288 (2013) 2441–2451. [DOI] [PMID: 23223233] |
|
[EC 3.1.3.91 created 2013] |
|
|
|
|
EC |
3.1.4.17 |
Accepted name: |
3′,5′-cyclic-nucleotide phosphodiesterase |
Reaction: |
nucleoside 3′,5′-cyclic phosphate + H2O = nucleoside 5′-phosphate |
Other name(s): |
cyclic 3′,5′-mononucleotide phosphodiesterase; PDE; cyclic 3′,5′-nucleotide phosphodiesterase; cyclic 3′,5′-phosphodiesterase; 3′,5′-nucleotide phosphodiesterase; 3′:5′-cyclic nucleotide 5′-nucleotidohydrolase; 3′,5′-cyclonucleotide phosphodiesterase; cyclic nucleotide phosphodiesterase; 3′, 5′-cyclic nucleoside monophosphate phosphodiesterase; 3′: 5′-monophosphate phosphodiesterase (cyclic CMP); cytidine 3′:5′-monophosphate phosphodiesterase (cyclic CMP); cyclic 3′,5-nucleotide monophosphate phosphodiesterase; nucleoside 3′,5′-cyclic phosphate diesterase; nucleoside-3′,5-monophosphate phosphodiesterase |
Systematic name: |
3′,5′-cyclic-nucleotide 5′-nucleotidohydrolase |
Comments: |
Acts on 3′,5′-cyclic AMP, 3′,5′-cyclic dAMP, 3′,5′-cyclic IMP, 3′,5′-cyclic GMP and 3′,5′-cyclic CMP. |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9040-59-9 |
References: |
1. |
Fischer, U. and Amrhein, N. Cyclic nucleotide phosphodiesterase of Chlamydomonas reinhardtii. Biochim. Biophys. Acta 341 (1974) 412–420. [DOI] [PMID: 4365506] |
2. |
Nair, K.G. Purification and properties of 3′,5′-cyclic nucleotide phosphodiesterase from dog heart. Biochemistry 5 (1966) 150–157. [PMID: 4287216] |
|
[EC 3.1.4.17 created 1972, modified 1976] |
|
|
|
|
EC |
3.1.4.35 |
Accepted name: |
3′,5′-cyclic-GMP phosphodiesterase |
Reaction: |
guanosine 3′,5′-cyclic phosphate + H2O = GMP |
Glossary: |
GMP = guanosine 5′-phosphate |
Other name(s): |
guanosine cyclic 3′,5′-phosphate phosphodiesterase; cyclic GMP phosphodiesterase; cyclic 3′,5′-GMP phosphodiesterase; cyclic guanosine 3′,5′-monophosphate phosphodiesterase; cyclic guanosine 3′,5′-phosphate phosphodiesterase; cGMP phosphodiesterase; cGMP-PDE |
Systematic name: |
3′,5′-cyclic-GMP 5′-nucleotidohydrolase |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9068-52-4 |
References: |
1. |
Marks, F. and Raab, I. The second messenger system of mouse epidermis. IV. Cyclic AMP and cyclic GMP phosphodiesterase. Biochim. Biophys. Acta 334 (1974) 368–377. |
|
[EC 3.1.4.35 created 1976] |
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|
|
|
EC |
3.1.4.52 |
Accepted name: |
cyclic-guanylate-specific phosphodiesterase |
Reaction: |
cyclic di-3′,5′-guanylate + H2O = 5′-phosphoguanylyl(3′→5′)guanosine |
|
For diagram of cyclic di-3′,5′-guanylate biosynthesis and breakdown, click here |
Glossary: |
c-di-GMP = c-di-guanylate = cyclic di-3′,5′-guanylate = cyclic-bis(3′→5′) dimeric GMP |
Other name(s): |
cyclic bis(3′→5′)diguanylate phosphodiesterase; c-di-GMP-specific phosphodiesterase; c-di-GMP phosphodiesterase; phosphodiesterase (misleading); phosphodiesterase A1; PDEA1; VieA |
Systematic name: |
cyclic bis(3′→5′)diguanylate 3′-guanylylhydrolase |
Comments: |
Requires Mg2+ or Mn2+ for activity and is inhibited by Ca2+ and Zn2+. Contains a heme unit. This enzyme linearizes cyclic di-3′,5′-guanylate, the product of EC 2.7.7.65, diguanylate cyclase and an allosteric activator of EC 2.4.1.12, cellulose synthase (UDP-forming), rendering it inactive [1]. It is the balance between these two enzymes that determines the cellular level of c-di-GMP [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 338732-46-0 |
References: |
1. |
Chang, A.L., Tuckerman, J.R., Gonzalez, G., Mayer, R., Weinhouse, H., Volman, G., Amikam, D., Benziman, M. and Gilles-Gonzalez, M.A. Phosphodiesterase A1, a regulator of cellulose synthesis in Acetobacter xylinum, is a heme-based sensor. Biochemistry 40 (2001) 3420–3426. [DOI] [PMID: 11297407] |
2. |
Christen, M., Christen, B., Folcher, M., Schauerte, A. and Jenal, U. Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP. J. Biol. Chem. 280 (2005) 30829–30837. [DOI] [PMID: 15994307] |
3. |
Schmidt, A.J., Ryjenkov, D.A. and Gomelsky, M. The ubiquitous protein domain EAL is a cyclic diguanylate-specific phosphodiesterase: enzymatically active and inactive EAL domains. J. Bacteriol. 187 (2005) 4774–4781. [DOI] [PMID: 15995192] |
4. |
Tamayo, R., Tischler, A.D. and Camilli, A. The EAL domain protein VieA is a cyclic diguanylate phosphodiesterase. J. Biol. Chem. 280 (2005) 33324–33330. [DOI] [PMID: 16081414] |
|
[EC 3.1.4.52 created 2008] |
|
|
|
|
EC |
3.1.4.53 |
Accepted name: |
3′,5′-cyclic-AMP phosphodiesterase |
Reaction: |
adenosine 3′,5′-cyclic phosphate + H2O = AMP |
Glossary: |
AMP = adenosine 5′-phosphate |
Other name(s): |
cAMP-specific phosphodiesterase; cAMP-specific PDE; PDE1; PDE2A; PDE2B; PDE4; PDE7; PDE8; PDEB1; PDEB2 |
Systematic name: |
3′,5′-cyclic-AMP 5′-nucleotidohydrolase |
Comments: |
Requires Mg2+ or Mn2+ for activity [2]. This enzyme is specific for 3′,5′-cAMP and does not hydrolyse other nucleoside 3′,5′-cyclic phosphates such as cGMP (cf. EC 3.1.4.17, 3,5-cyclic-nucleotide phosphodiesterase and EC 3.1.4.35, 3,5-cyclic-GMP phosphodiesterase). It is involved in modulation of the levels of cAMP, which is a mediator in the processes of cell transformation and proliferation [3]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Alonso, G.D., Schoijet, A.C., Torres, H.N. and Flawiá, M.M. TcPDE4, a novel membrane-associated cAMP-specific phosphodiesterase from Trypanosoma cruzi. Mol. Biochem. Parasitol. 145 (2006) 40–49. [DOI] [PMID: 16225937] |
2. |
Bader, S., Kortholt, A., Snippe, H. and Van Haastert, P.J. DdPDE4, a novel cAMP-specific phosphodiesterase at the surface of Dictyostelium cells. J. Biol. Chem. 281 (2006) 20018–20026. [DOI] [PMID: 16644729] |
3. |
Rascón, A., Soderling, S.H., Schaefer, J.B. and Beavo, J.A. Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei. Proc. Natl. Acad. Sci. USA 99 (2002) 4714–4719. [DOI] [PMID: 11930017] |
4. |
Johner, A., Kunz, S., Linder, M., Shakur, Y. and Seebeck, T. Cyclic nucleotide specific phosphodiesterases of Leishmania major. BMC Microbiol. 6:25 (2006). [DOI] [PMID: 16522215] |
5. |
Lugnier, C., Keravis, T., Le Bec, A., Pauvert, O., Proteau, S. and Rousseau, E. Characterization of cyclic nucleotide phosphodiesterase isoforms associated to isolated cardiac nuclei. Biochim. Biophys. Acta 1472 (1999) 431–446. [DOI] [PMID: 10564757] |
6. |
Imamura, R., Yamanaka, K., Ogura, T., Hiraga, S., Fujita, N., Ishihama, A. and Niki, H. Identification of the cpdA gene encoding cyclic 3′,5′-adenosine monophosphate phosphodiesterase in Escherichia coli. J. Biol. Chem. 271 (1996) 25423–25429. [DOI] [PMID: 8810311] |
|
[EC 3.1.4.53 created 2008, modified 2011] |
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|
|
|
EC
|
3.1.11.8
|
Transferred entry: | guanosine-5′-diphospho-5′-[DNA] diphosphatase. Now EC 3.6.1.70, guanosine-5′-diphospho-5′-[DNA] diphosphatase
|
[EC 3.1.11.8 created 2017, deleted 2019] |
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|
|
|
EC
|
3.1.12.2
|
Transferred entry: | DNA-3-diphospho-5-guanosine diphosphatase. Now EC 3.6.1.72, DNA-3-diphospho-5-guanosine diphosphatase
|
[EC 3.1.12.2 created 2017, deleted 2019] |
|
|
|
|
EC |
3.6.1.17 |
Accepted name: |
bis(5′-nucleosyl)-tetraphosphatase (asymmetrical) |
Reaction: |
P1,P4-bis(5′-guanosyl) tetraphosphate + H2O = GTP + GMP |
Other name(s): |
bis(5′-guanosyl)-tetraphosphatase; bis(5′-adenosyl)-tetraphosphatase; diguanosinetetraphosphatase (asymmetrical); dinucleosidetetraphosphatase (asymmetrical); diadenosine P1,P4-tetraphosphatase; dinucleoside tetraphosphatase; 1-P,4-P-bis(5′-nucleosyl)-tetraphosphate nucleotidohydrolase |
Systematic name: |
P1,P4-bis(5′-nucleosyl)-tetraphosphate nucleotidohydrolase |
Comments: |
Also acts on bis(5′-xanthosyl)-tetraphosphate and, more slowly, on bis(5′-adenosyl)-tetraphosphate and bis(5′-uridyl)-tetraphosphate [cf. EC 3.6.1.41 bis(5′-nucleosyl)-tetraphosphatase (symmetrical)] |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37289-29-5 |
References: |
1. |
Jakubowski, H. and Guranowski, A. Enzymes hydrolyzing ApppA and/or AppppA in higher plants. Purification and some properties of diadenosine triphosphatase, diadenosine tetraphosphatase, and phosphodiesterase from yellow lupin (Lupinus luteus) seeds. J. Biol. Chem. 258 (1983) 9982–9989. [PMID: 6309793] |
2. |
Vallejo, C.M., Lobatón, C.D., Quintanilla, M., Sillero, A. and Sillero, M.A.G. Dinucleosidasetetraphosphatase in rat liver and Artemia salina. Biochim. Biophys. Acta 438 (1976) 304–309. [DOI] [PMID: 181087] |
3. |
Warner, A.H. and Finamore, F.J. Isolation, purification, and characterization of P1,P4-diguanosine 5′-tetraphosphate asymmetrical-pyrophosphohydrolase from brine shrimp eggs. Biochemistry 4 (1965) 1568–1575. [PMID: 4955726] |
|
[EC 3.6.1.17 created 1972, modified 1976, modified 1986] |
|
|
|
|
EC |
3.6.1.42 |
Accepted name: |
guanosine-diphosphatase |
Reaction: |
GDP + H2O = GMP + phosphate |
Other name(s): |
GDPase |
Systematic name: |
GDP phosphohydrolase |
Comments: |
Also acts on UDP but not on other nucleoside diphosphates and triphosphates. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 98037-56-0 |
References: |
1. |
Raychaudhuri, P., Ghosh, S. and Maitra, U. Purification and characterization of a guanosine diphosphatase activity from calf liver microsomal salt wash proteins. J. Biol. Chem. 260 (1985) 8306–8311. [PMID: 2989286] |
|
[EC 3.6.1.42 created 1989] |
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|
|
|
EC |
3.6.1.55 |
Accepted name: |
8-oxo-dGTP diphosphatase |
Reaction: |
8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate |
Glossary: |
8-oxo-dGTP = 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate |
Other name(s): |
MutT; 7,8-dihydro-8-oxoguanine triphosphatase; 8-oxo-dGTPase; 7,8-dihydro-8-oxo-dGTP pyrophosphohydrolase |
Systematic name: |
8-oxo-dGTP diphosphohydrolase |
Comments: |
This enzyme hydrolyses the phosphoanhydride bond between the α and β phosphate of 8-oxoguanine-containing nucleoside di- and triphosphates thereby preventing misincorporation of the oxidized purine nucleoside triphosphates into DNA. It does not hydrolyse 2-hydroxy-dATP (cf. EC 3.6.1.56, 2-hydroxy-dATP diphosphatase) [4]. Requires Mg2+. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Ito, R., Hayakawa, H., Sekiguchi, M. and Ishibashi, T. Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools. Biochemistry 44 (2005) 6670–6674. [DOI] [PMID: 15850400] |
2. |
Yoshimura, K., Ogawa, T., Ueda, Y. and Shigeoka, S. AtNUDX1, an 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase, is responsible for eliminating oxidized nucleotides in Arabidopsis. Plant Cell Physiol. 48 (2007) 1438–1449. [DOI] [PMID: 17804481] |
3. |
Nakamura, T., Meshitsuka, S., Kitagawa, S., Abe, N., Yamada, J., Ishino, T., Nakano, H., Tsuzuki, T., Doi, T., Kobayashi, Y., Fujii, S., Sekiguchi, M. and Yamagata, Y. Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. J. Biol. Chem. 285 (2010) 444–452. [DOI] [PMID: 19864691] |
4. |
Yonekura, S., Sanada, U. and Zhang-Akiyama, Q.M. CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis. Genes Genet. Syst. 85 (2010) 287–295. [PMID: 21178309] |
|
[EC 3.6.1.55 created 2011] |
|
|
|
|
EC |
3.6.1.58 |
Accepted name: |
8-oxo-dGDP phosphatase |
Reaction: |
(1) 8-oxo-dGDP + H2O = 8-oxo-dGMP + phosphate (2) 8-oxo-GDP + H2O = 8-oxo-GMP + phosphate |
Glossary: |
8-oxo-dGDP = 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-diphosphate |
Other name(s): |
NUDT5; MTH3 (gene name); NUDT18 |
Systematic name: |
8-oxo-dGDP phosphohydrolase |
Comments: |
The enzyme catalyses the hydrolysis of both 8-oxo-dGDP and 8-oxo-GDP thereby preventing translational errors caused by oxidative damage. The preferred in vivo substrate is not known. The enzyme does not degrade 8-oxo-dGTP and 8-oxo-GTP to the monophosphates (cf. EC 3.6.1.55, 8-oxo-dGTP diphosphatase) [1,2]. Ribonucleotide diphosphates and deoxyribonucleotide diphosphates are hydrolysed with broad specificity. The bifunctional enzyme NUDT5 also hydrolyses ADP-ribose to AMP and D-ribose 5-phosphate (cf. EC 3.6.1.13, ADP-ribose diphosphatase) [4]. The human enzyme NUDT18 also hydrolyses 8-oxo-dADP and 2-hydroxy-dADP, the latter at a slower rate [6]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Ishibashi, T., Hayakawa, H., Ito, R., Miyazawa, M., Yamagata, Y. and Sekiguchi, M. Mammalian enzymes for preventing transcriptional errors caused by oxidative damage. Nucleic Acids Res. 33 (2005) 3779–3784. [DOI] [PMID: 16002790] |
2. |
Ishibashi, T., Hayakawa, H. and Sekiguchi, M. A novel mechanism for preventing mutations caused by oxidation of guanine nucleotides. EMBO Rep. 4 (2003) 479–483. [DOI] [PMID: 12717453] |
3. |
Kamiya, H., Hori, M., Arimori, T., Sekiguchi, M., Yamagata, Y. and Harashima, H. NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity. DNA Repair (Amst) 8 (2009) 1250–1254. [DOI] [PMID: 19699693] |
4. |
Ito, R., Sekiguchi, M., Setoyama, D., Nakatsu, Y., Yamagata, Y. and Hayakawa, H. Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein. J. Biochem. 149 (2011) 731–738. [DOI] [PMID: 21389046] |
5. |
Zha, M., Zhong, C., Peng, Y., Hu, H. and Ding, J. Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity. J. Mol. Biol. 364 (2006) 1021–1033. [DOI] [PMID: 17052728] |
6. |
Takagi, Y., Setoyama, D., Ito, R., Kamiya, H., Yamagata, Y. and Sekiguchi, M. Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2. J. Biol. Chem. 287 (2012) 21541–21549. [DOI] [PMID: 22556419] |
|
[EC 3.6.1.58 created 2012] |
|
|
|
|
EC |
3.6.1.59 |
Accepted name: |
5′-(N7-methyl 5′-triphosphoguanosine)-[mRNA] diphosphatase |
Reaction: |
a 5′-(N7-methyl 5′-triphosphoguanosine)-[mRNA] + H2O = N7-methylguanosine 5′-phosphate + a 5′-diphospho-[mRNA] |
Other name(s): |
DcpS; m7GpppX pyrophosphatase; m7GpppN m7GMP phosphohydrolase; m7GpppX diphosphatase; m7G5′ppp5’N m7GMP phosphohydrolase |
Systematic name: |
5′-(N7-methyl 5′-triphosphoguanosine)-[mRNA] N7-methylguanosine 5′-phosphate phosphohydrolase |
Comments: |
The enzyme removes (decaps) the N7-methylguanosine 5-phosphate cap from an mRNA degraded to a maximal length of 10 nucleotides [3,6]. Decapping is an important process in the control of eukaryotic mRNA degradation. The enzyme functions to clear the cell of cap structure following decay of the RNA body [2]. The nematode enzyme can also decap triply methylated substrates, 5′-(N2,N2,N7-trimethyl 5′-triphosphoguanosine)-[mRNA] [4].
|
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Malys, N. and McCarthy, J.E. Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies. J. Mol. Biol. 363 (2006) 370–382. [DOI] [PMID: 16963086] |
2. |
Liu, S.W., Rajagopal, V., Patel, S.S. and Kiledjian, M. Mechanistic and kinetic analysis of the DcpS scavenger decapping enzyme. J. Biol. Chem. 283 (2008) 16427–16436. [DOI] [PMID: 18441014] |
3. |
Liu, H., Rodgers, N.D., Jiao, X. and Kiledjian, M. The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J. 21 (2002) 4699–4708. [DOI] [PMID: 12198172] |
4. |
van Dijk, E., Le Hir, H. and Seraphin, B. DcpS can act in the 5′-3′ mRNA decay pathway in addition to the 3′-5′ pathway. Proc. Natl. Acad. Sci. USA 100 (2003) 12081–12086. [DOI] [PMID: 14523240] |
5. |
Chen, N., Walsh, M.A., Liu, Y., Parker, R. and Song, H. Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping. J. Mol. Biol. 347 (2005) 707–718. [DOI] [PMID: 15769464] |
6. |
Cohen, L.S., Mikhli, C., Friedman, C., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E. and Davis, R.E. Nematode m7GpppG and m3(2,2,7)GpppG decapping: activities in Ascaris embryos and characterization of C. elegans scavenger DcpS. RNA 10 (2004) 1609–1624. [DOI] [PMID: 15383679] |
7. |
Wypijewska, A., Bojarska, E., Lukaszewicz, M., Stepinski, J., Jemielity, J., Davis, R.E. and Darzynkiewicz, E. 7-Methylguanosine diphosphate (m7GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry 51 (2012) 8003–8013. [DOI] [PMID: 22985415] |
|
[EC 3.6.1.59 created 2012, modified 2013] |
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|
|
|
EC |
3.6.1.70 |
Accepted name: |
guanosine-5′-diphospho-5′-[DNA] diphosphatase |
Reaction: |
guanosine-5′-diphospho-5′-[DNA] + H2O = phospho-5′-[DNA] + GMP |
Other name(s): |
aprataxin; pp5′G5′DNA diphosphatase; pp5′G5′-DNA guanylate hydrolase; APTX (gene name); HNT3 (gene name) |
Systematic name: |
guanosine-5′-diphospho-5′-[DNA] hydrolase (guanosine 5′-phosphate-forming) |
Comments: |
Aprataxin is a DNA-binding protein that catalyses (among other activities) the 5′ decapping of Gpp-DNA (formed by homologs of RtcB3 from the bacterium Myxococcus xanthus). The enzyme binds the guanylate group to a histidine residue at its active site, forming a covalent enzyme-nucleotide phosphate intermediate, followed by the hydrolysis of the guanylate from the nucleic acid and eventual release. The enzyme forms a 5′-phospho terminus that can be efficiently joined by "classical" ligases. The enzyme also possesses the activitiy of EC 3.6.1.71, adenosine-5′-diphospho-5′-[DNA] diphosphatase and EC 3.6.1.72, DNA-3′-diphospho-5′-guanosine diphosphatase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Maughan, W.P. and Shuman, S. Characterization of 3′-phosphate RNA ligase paralogs RtcB1, RtcB2, and RtcB3 from Myxococcus xanthus highlights DNA and RNA 5′-phosphate capping activity of RtcB3. J. Bacteriol. 197 (2015) 3616–3624. [DOI] [PMID: 26350128] |
|
[EC 3.6.1.70 created 2017 as EC 3.1.11.8, transferred 2019 to EC 3.6.1.70] |
|
|
|
|
EC |
3.6.1.72 |
Accepted name: |
DNA-3′-diphospho-5′-guanosine diphosphatase |
Reaction: |
[DNA]-3′-diphospho-5′-guanosine + H2O = [DNA]-3′-phosphate + GMP |
Other name(s): |
aprataxin; DNA-3′pp5′G guanylate hydrolase; APTX (gene name); HNT3 (gene name) |
Systematic name: |
[DNA]-3′-diphospho-5′-guanosine hydrolase (guanosine 5′-phosphate-forming) |
Comments: |
Aprataxin is a DNA-binding protein that catalyses (among other activities) the 3′ decapping of DNA-ppG (formed by EC 6.5.1.8, 3′-phosphate/5′-hydroxy nucleic acid ligase) [1]. The enzyme binds the guanylate group to a histidine residue at its active site, forming a covalent enzyme-nucleotide phosphate intermediate, followed by the hydrolysis of the guanylate from the nucleic acid and its eventual release. The enzyme also possesses the activity of EC 3.6.1.71, adenosine-5′-diphospho-5′-[DNA] diphosphatase, and EC 3.6.1.70, guanosine-5′-diphospho-5′-[DNA] diphosphatase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Das, U., Chauleau, M., Ordonez, H. and Shuman, S. Impact of DNA3′pp5′G capping on repair reactions at DNA 3′ ends. Proc. Natl. Acad. Sci. USA 111 (2014) 11317–11322. [DOI] [PMID: 25049385] |
2. |
Chauleau, M., Jacewicz, A. and Shuman, S. DNA3′pp5′G de-capping activity of aprataxin: effect of cap nucleoside analogs and structural basis for guanosine recognition. Nucleic Acids Res. 43 (2015) 6075–6083. [DOI] [PMID: 26007660] |
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[EC 3.6.1.72 created 2017 as EC 3.1.12.2, transferred 2019 to EC 3.6.1.72] |
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|
|
|
EC |
3.6.5.1 |
Accepted name: |
heterotrimeric G-protein GTPase |
Reaction: |
GTP + H2O = GDP + phosphate |
Systematic name: |
GTP phosphohydrolase (signalling) |
Comments: |
This group comprises GTP-hydrolysing systems, where GTP and GDP alternate in binding. This group includes stimulatory and inhibitory G-proteins such as Gs, Gi, Go and Golf, targetting adenylate cyclase and/or K+ and Ca2+ channels; Gq stimulating phospholipase C; transducin activating cGMP phosphodiesterase; gustducin activating cAMP phosphodiesterase. Golf is instrumental in odour perception, transducin in vision and gustducin in taste recognition. At least 16 different α subunits (39-52 kDa), 5 β subunits (36 kDa) and 12 γ subunits (6-9 kDa) are known. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Neer, E.J. Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80 (1995) 249–259. [DOI] [PMID: 7834744] |
2. |
Sprang, S.R. G protein mechanisms: insights from structural analysis. Annu. Rev. Biochem. 66 (1997) 639–678. [DOI] [PMID: 9242920] |
3. |
Bondarenko, V.A., Deasi, M., Dua, S., Yamazaki, M., Amin, R.H., Yousif, K.K., Kinumi, T., Ohashi, M., Komori, N., Matsumoto, H., Jackson, K.W., Hayashi, F., Usukura, J., Lipikin, V.M. and Yamazaki, A. Residues within the polycationic region of cGMP phosphodiesterase γ subunit crucial for the interaction with transducin α subunit. Identification by endogenous ADP-ribosylation and site-directed mutagenesis. J. Biol. Chem. 272 (1997) 15856–15864. [DOI] [PMID: 9188484] |
4. |
Ming, D., Ruiz-Avila, L. and Margolskee, R.F. Characterization and solubilization of bitter-responsive receptors that couple to gustducin. Proc. Natl. Acad. Sci. USA 95 (1998) 8933–8938. [DOI] [PMID: 9671782] |
|
[EC 3.6.5.1 created 2000 as EC 3.6.1.46, transferred 2003 to EC 3.6.5.1] |
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|
|
|
EC |
4.3.2.2 |
Accepted name: |
adenylosuccinate lyase |
Reaction: |
(1) N6-(1,2-dicarboxyethyl)AMP = fumarate + AMP (2) (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide |
|
For diagram of AMP and GMP biosynthesis, click here and for diagram of the late stages of purine biosynthesis, click here |
Other name(s): |
adenylosuccinase; succino AMP-lyase; 6-N-(1,2-dicarboxyethyl)AMP AMP-lyase; 6-N-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) |
Systematic name: |
N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) |
Comments: |
Also acts on 1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole. |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9027-81-0 |
References: |
1. |
Carter, C.E. and Cohen, L.H. The preparation and properties of adenylosuccinase and adenylosuccinic acid. J. Biol. Chem. 222 (1956) 17–30. [PMID: 13366975] |
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[EC 4.3.2.2 created 1961, modified 2000] |
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|
EC |
4.6.1.2 |
Accepted name: |
guanylate cyclase |
Reaction: |
GTP = 3′,5′-cyclic GMP + diphosphate |
|
For diagram of GTP biosynthesis, click here |
Other name(s): |
guanylyl cyclase; guanyl cyclase; GTP diphosphate-lyase (cyclizing) |
Systematic name: |
GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming) |
Comments: |
Also acts on ITP and dGTP. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9054-75-5 |
References: |
1. |
Garbers, D.L., Suddath, J.L. and Hardman, J.G. Enzymatic formation of inosine 3′,5′-monophosphate and of 2′-deoxyguanosine 3′,5′-monophosphate. Inosinate and deoxyguanylate cyclase activity. Biochim. Biophys. Acta 377 (1975) 174–185. [DOI] [PMID: 235291] |
2. |
Hardman, J.G. and Sutherland, E.W. Guanyl cyclase, an enzyme catalyzing the formation of guanosine 3′,5′-monophosphate from guanosine triphosphate. J. Biol. Chem. 244 (1969) 6363–6370. [PMID: 4982201] |
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[EC 4.6.1.2 created 1972] |
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|
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] |
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|
EC |
6.3.4.4 |
Accepted name: |
adenylosuccinate synthase |
Reaction: |
GTP + IMP + L-aspartate = GDP + phosphate + N6-(1,2-dicarboxyethyl)-AMP |
|
For diagram of AMP and GMP biosynthesis, click here |
Other name(s): |
IMP—aspartate ligase; adenylosuccinate synthetase; succinoadenylic kinosynthetase; succino-AMP synthetase |
Systematic name: |
IMP:L-aspartate ligase (GDP-forming) |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9023-57-8 |
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. [DOI] [PMID: 13662023] |
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[EC 6.3.4.4 created 1961] |
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EC |
6.3.4.25 |
Accepted name: |
2-amino-2′-deoxyadenylo-succinate synthase |
Reaction: |
ATP + dGMP + L-aspartate = ADP + phosphate + 2-amino-2′-deoxy-N6-[(2S)-succino]adenylate |
Glossary: |
dZTP = 2-amino-2′-deoxyadenosine 5′-triphosphate |
Other name(s): |
purZ (gene name) |
Systematic name: |
dGMP:L-aspartate ligase (ADP-forming) |
Comments: |
The enzyme, characterized from a number of bacteriophages, participates in the biosynthesis of dZTP, which replaces dATP in the genome of these phages. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Zhou, Y., Xu, X., Wei, Y., Cheng, Y., Guo, Y., Khudyakov, I., Liu, F., He, P., Song, Z., Li, Z., Gao, Y., Ang, E.L., Zhao, H., Zhang, Y. and Zhao, S. A widespread pathway for substitution of adenine by diaminopurine in phage genomes. Science 372 (2021) 512–516. [DOI] [PMID: 33926954] |
2. |
Sleiman, D., Garcia, P.S., Lagune, M., Loc'h, J., Haouz, A., Taib, N., Rothlisberger, P., Gribaldo, S., Marliere, P. and Kaminski, P.A. A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes. Science 372 (2021) 516–520. [DOI] [PMID: 33926955] |
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[EC 6.3.4.25 created 2021] |
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|
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 |
|
For diagram of AMP and GMP biosynthesis, click here |
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. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37318-71-1 |
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. [DOI] [PMID: 17103135] |
|
[EC 6.3.5.2 created 1961, modified 2013] |
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|
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). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
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. [DOI] [PMID: 22074260] |
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[EC 6.5.1.5 created 2013, modified 2016] |
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|
|
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. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
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. [DOI] [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. [DOI] [PMID: 23546841] |
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[EC 6.5.1.7 created 2014, modified 2016] |
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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]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [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. [DOI] [PMID: 26858100] |
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[EC 6.5.1.8 created 2017] |
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