EC |
2.1.1.45 |
Accepted name: |
thymidylate synthase |
Reaction: |
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP |
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For diagram of C1 metabolism, click here |
Other name(s): |
dTMP synthase; thymidylate synthetase; methylenetetrahydrofolate:dUMP C-methyltransferase; TMP synthetase |
Systematic name: |
5,10-methylenetetrahydrofolate:dUMP C-methyltransferase |
Links to other databases: |
BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9031-61-2 |
References: |
1. |
Blakley, R.L. The biosynthesis of thymidylic acid. IV. Further studies on thymidylate synthase. J. Biol. Chem. 238 (1963) 2113–2118. |
2. |
Lockshin, A., Moran, R.G. and Danenberg, P.V. Thymidylate synthetase purified to homogeneity from human leukemic cells. Proc. Natl. Acad. Sci. USA 76 (1979) 750–754. [DOI] [PMID: 34155] |
3. |
Slavik, K. and Slavikova, V. Purification of thymidylate synthetase from enzyme-poor sources by affinity chromatography. Methods Enzymol. 66 (1980) 709–723. [PMID: 6990200] |
4. |
Wahba, A.J. and Friedkin, M. The enzymatic synthesis of thymidylate. I. Early steps in the purification of thymidylate synthetase of Escherichia coli. J. Biol. Chem. 237 (1962) 3794–3801. [PMID: 13998281] |
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[EC 2.1.1.45 created 1976] |
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EC |
2.1.1.148 |
Accepted name: |
thymidylate synthase (FAD) |
Reaction: |
5,10-methylenetetrahydrofolate + dUMP + NADPH + H+ = dTMP + tetrahydrofolate + NADP+ |
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For diagram of C1 metabolism, click here |
Other name(s): |
Thy1; ThyX |
Systematic name: |
5,10-methylenetetrahydrofolate,FADH2:dUMP C-methyltransferase |
Comments: |
Contains FAD. All thymidylate synthases catalyse a reductive methylation involving the transfer of the methylene group of 5,10-methylenetetrahydrofolate to the C5 position of dUMP and a two electron reduction of the methylene group to a methyl group. Unlike the classical thymidylate synthase, ThyA (EC 2.1.1.45), which uses folate as both a 1-carbon donor and a source of reducing equivalents, this enzyme uses a flavin cofactor as a source of reducing equivalents, which are derived from NADPH. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 850167-13-4 |
References: |
1. |
Myllykallio, H., Lipowski, G., Leduc, D., Filee, J., Forterre, P. and Liebl, U. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297 (2002) 105–107. [DOI] [PMID: 12029065] |
2. |
Griffin, J., Roshick, C., Iliffe-Lee, E. and McClarty, G. Catalytic mechanism of Chlamydia trachomatis flavin-dependent thymidylate synthase. J. Biol. Chem. 280 (2005) 5456–5467. [DOI] [PMID: 15591067] |
3. |
Graziani, S., Bernauer, J., Skouloubris, S., Graille, M., Zhou, C.Z., Marchand, C., Decottignies, P., van Tilbeurgh, H., Myllykallio, H. and Liebl, U. Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX. J. Biol. Chem. 281 (2006) 24048–24057. [DOI] [PMID: 16707489] |
4. |
Koehn, E.M., Fleischmann, T., Conrad, J.A., Palfey, B.A., Lesley, S.A., Mathews, I.I. and Kohen, A. An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene. Nature 458 (2009) 919–923. [DOI] [PMID: 19370033] |
5. |
Koehn, E.M. and Kohen, A. Flavin-dependent thymidylate synthase: a novel pathway towards thymine. Arch. Biochem. Biophys. 493 (2010) 96–102. [DOI] [PMID: 19643076] |
6. |
Mishanina, T.V., Yu, L., Karunaratne, K., Mondal, D., Corcoran, J.M., Choi, M.A. and Kohen, A. An unprecedented mechanism of nucleotide methylation in organisms containing thyX. Science 351 (2016) 507–510. [DOI] [PMID: 26823429] |
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[EC 2.1.1.148 created 2003, modified 2010] |
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EC |
2.7.1.21 |
Accepted name: |
thymidine kinase |
Reaction: |
ATP + thymidine = ADP + dTMP |
Glossary: |
dTMP = thymidine 5′-phosphate |
Other name(s): |
thymidine kinase (phosphorylating); 2′-deoxythymidine kinase; deoxythymidine kinase (phosphorylating) |
Systematic name: |
ATP:thymidine 5′-phosphotransferase |
Comments: |
Deoxyuridine can also act as acceptor, and dGTP can act as a donor. The deoxypyrimidine kinase complex induced by Herpes simplex virus catalyses this reaction as well as those of EC 2.7.1.114 (AMP—thymidine kinase), EC 2.7.1.118 (ADP—thymidine kinase) and EC 2.7.4.9 (dTMP-kinase). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9002-06-6 |
References: |
1. |
Falke, D., Labenz, J., Brauer, D. and Muller, W.E.G. Adenosine diphosphate: thymidine 5′-phosphotransferase, a new enzyme activity, associated with the Herpes simplex virus-induced deoxypyrimidine kinase. Biochim. Biophys. Acta 708 (1982) 99–103. [DOI] [PMID: 6293576] |
2. |
Kizer, D.E. and Holman, L. Purification and properties of thymidine kinase from regenerating rat liver. Biochim. Biophys. Acta 350 (1974) 193–200. [DOI] [PMID: 4407348] |
3. |
Okazaki, R. and Kornberg, A. Deoxythymidine kinase of Escherichia coli. I. Purification and some properties of the enzyme. J. Biol. Chem. 239 (1964) 269–274. [PMID: 14114853] |
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[EC 2.7.1.21 created 1961, deleted 1972, reinstated 1976 (EC 2.7.1.75 created 1972, incorporated 1976)] |
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EC |
2.7.1.114 |
Accepted name: |
AMP—thymidine kinase |
Reaction: |
AMP + thymidine = adenosine + dTMP |
Glossary: |
dTMP = thymidine 5′-phosphate |
Other name(s): |
adenylate-nucleoside phosphotransferase |
Systematic name: |
AMP:thymidine 5′-phosphotransferase |
Comments: |
The deoxypyrimidine kinase complex induced by Herpes simplex virus catalyses this reaction as well as those of EC 2.7.1.21 (thymidine kinase), EC 2.7.1.118 (ADP—thymidine kinase) and EC 2.7.4.9 (dTMP kinase). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 60440-28-0 |
References: |
1. |
Falke, D., Labenz, J., Brauer, D. and Muller, W.E.G. Adenosine diphosphate: thymidine 5′-phosphotransferase, a new enzyme activity, associated with the Herpes simplex virus-induced deoxypyrimidine kinase. Biochim. Biophys. Acta 708 (1982) 99–103. [DOI] [PMID: 6293576] |
2. |
Falke, D., Nehrbass, W., Brauer, D. and Mueller, W.E.G. Adenylic acid: deoxythymidine 5′-phosphotransferase: evidence for the existence of a novel Herpes simplex virus-induced enzyme. J. Gen. Virol. 53 (1981) 247–255. [DOI] [PMID: 6267178] |
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[EC 2.7.1.114 created 1984] |
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EC |
2.7.1.118 |
Accepted name: |
ADP—thymidine kinase |
Reaction: |
ADP + thymidine = AMP + dTMP |
Glossary: |
dTMP = thymidine 5′-phosphate |
Other name(s): |
ADP:dThd phosphotransferase; adenosine diphosphate-thymidine phosphotransferase |
Systematic name: |
ADP:thymidine 5′-phosphotransferase |
Comments: |
The deoxypyrimidine kinase complex induced by Herpes simplex virus catalyses this reaction as well as those of EC 2.7.1.21 (thymidine kinase), EC 2.7.1.114 (AMP—thymidine kinase) and EC 2.7.4.9 (dTMP kinase). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 82114-39-4 |
References: |
1. |
Falke, D., Labenz, J., Brauer, D. and Muller, W.E.G. Adenosine diphosphate: thymidine 5′-phosphotransferase, a new enzyme activity, associated with the Herpes simplex virus-induced deoxypyrimidine kinase. Biochim. Biophys. Acta 708 (1982) 99–103. [DOI] [PMID: 6293576] |
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[EC 2.7.1.118 created 1986] |
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EC |
2.7.4.9 |
Accepted name: |
dTMP kinase |
Reaction: |
ATP + dTMP = ADP + dTDP |
Other name(s): |
thymidine monophosphate kinase; thymidylate kinase; thymidylate monophosphate kinase; thymidylic acid kinase; thymidylic kinase; deoxythymidine 5′-monophosphate kinase; TMPK; thymidine 5′-monophosphate kinase |
Systematic name: |
ATP:dTMP phosphotransferase |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9014-43-1 |
References: |
1. |
Hurwitz, J. The enzymatic incorporation of ribonucleotides into polydeoxynucleotide material. J. Biol. Chem. 234 (1959) 2351–2358. [PMID: 14405566] |
2. |
Keilley, R.K. Purification and properties of thymidine monophosphate kinase from mouse hepatoma. J. Biol. Chem. 245 (1970) 4204–4212. [PMID: 4323166] |
3. |
Nelson, D.J. and Carter, C.E. Purification and characterization of thymidine 5-monophosphate kinase from Escherichia coli B. J. Biol. Chem. 244 (1969) 5254–5262. [PMID: 4899016] |
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[EC 2.7.4.9 created 1965] |
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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] |
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[EC 2.7.4.12 created 1972] |
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EC |
3.1.3.35 |
Accepted name: |
thymidylate 5′-phosphatase |
Reaction: |
thymidylate + H2O = thymidine + phosphate |
Other name(s): |
thymidylate 5′-nucleotidase; deoxythymidylate 5′-nucleotidase; thymidylate nucleotidase; deoxythymidylic 5′-nucleotidase; deoxythymidylate phosphohydrolase; dTMPase |
Systematic name: |
thymidylate 5′-phosphohydrolase |
Comments: |
Acts on 5-methyl-dCMP and on TMP, but more slowly than on dTMP. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9026-80-6 |
References: |
1. |
Aposhian, H.V. and Tremblay, G.Y. Deoxythymidylate 5′-nucleotidase. Purification and properties of an enzyme found after infection of Bacillus subtilis with phage SP5C. J. Biol. Chem. 241 (1966) 5095–5101. [PMID: 4958986] |
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[EC 3.1.3.35 created 1972] |
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EC |
3.2.2.10 |
Accepted name: |
pyrimidine-5′-nucleotide nucleosidase |
Reaction: |
a pyrimidine 5′-nucleotide + H2O = D-ribose 5-phosphate + a pyrimidine base |
Other name(s): |
pyrimidine nucleotide N-ribosidase; Pyr5N |
Systematic name: |
pyrimidine-5′-nucleotide phosphoribo(deoxyribo)hydrolase |
Comments: |
Also acts on dUMP, dTMP and dCMP. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9023-31-8 |
References: |
1. |
Imada, A. Degradation of pyrimidine nucleotides by enzyme systems of Streptomyces. II. Pyrimidine 5′-nucleotide phosphoribo(deoxyribo) hydrolase of Streptomyces virginiae. J. Gen. Appl. Microbiol. 13 (1967) 267–278. |
2. |
Imada, A., Kuno, M. and Igarasi, S. Degradation of pyrimidine nucleotides by enzyme systems of Streptomyces. I. Ribose-5-phosphate formation from pyrimidine nucleotides. J. Gen. Appl. Microbiol. 13 (1967) 255–265. |
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[EC 3.2.2.10 created 1972] |
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