Thymidylate synthase

Thymidylate synthetase
File:Thymidylate synthase 1HVY.png Ribbon diagram of human thymidylate synthase in complex with dUMP (orange) and raltitrexed (lime green). From PDB: 1HVY​.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1hvy​, 1hw3​, 1hw4​, 1hzw​, 1i00​, 1ju6​, 1juj​, 1ypv​, 2onb​
Identifiers
Symbols	TYMS ; TS; HsT422; MGC88736; TMS; TSase
External IDs	Template:OMIM5 Template:MGI HomoloGene: 834
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE TYMS 202589 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Thymidylate synthase (EC 2.1.1.45) is the enzyme used to generate thymidine monophosphate (dTMP), which is subsequently phosphorylated to thymidine triphosphate for use in DNA synthesis and repair. By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product.

As an anti-cancer chemotherapy target, thymidylate synthase can be inhibited by the fluorinated pyrimidine fluorouracil, or certain folate analogues, including most notably raltitrexed (trade name Tomudex).

See also

• Pyrimidine analogues

Further reading

• Carreras CW, and Santi DV (1995). "The Catalytic Mechanism and Structure of Thymidylate Synthase". Annual Review of Biochemistry. 64 (1): 721–762. PMID 7574499.
• Banerjee D, Mayer-Kuckuk P, Capiaux G; et al. (2002). "Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase". Biochim. Biophys. Acta. 1587 (2–3): 164–73. PMID 12084458.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Liu J, Schmitz JC, Lin X; et al. (2002). "Thymidylate synthase as a translational regulator of cellular gene expression". Biochim. Biophys. Acta. 1587 (2–3): 174–82. PMID 12084459.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Chu J, Dolnick BJ (2002). "Natural antisense (rTSalpha) RNA induces site-specific cleavage of thymidylate synthase mRNA". Biochim. Biophys. Acta. 1587 (2–3): 183–93. PMID 12084460.
• Peters GJ, Backus HH, Freemantle S; et al. (2002). "Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism". Biochim. Biophys. Acta. 1587 (2–3): 194–205. PMID 12084461.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Costi MP, Tondi D, Rinaldi M; et al. (2002). "Structure-based studies on species-specific inhibition of thymidylate synthase". Biochim. Biophys. Acta. 1587 (2–3): 206–14. PMID 12084462.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Lin D, Li H, Tan W; et al. (2007). "Genetic polymorphisms in folate- metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development". Forum of nutrition. 60: 140–5. doi:10.1159/0000107090. PMID 17684410.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• Thymidylate+synthase at the US National Library of Medicine Medical Subject Headings (MeSH)