Thymidylate synthase

Thymidylate synthetase
Ribbon diagram of human thymidylate synthetase in complex with dUMP (orange) and raltitrexed (lime green). From PDB 1HVY.
Available structures
1hvy, 1hw3, 1hw4, 1hzw, 1i00, 1ju6, 1juj, 1ypv, 2onb
Identifiers
Symbols	TYMS; TS; HsT422; MGC88736; TMS; TSase
External IDs	OMIM: 188350 MGI: 98878 HomoloGene: 834
Gene ontology Molecular function • thymidylate synthase activity • methyltransferase activity • transferase activity Biological process • nucleobase, nucleoside, nucleotide and nucleic acid metabolic process • dTMP biosynthetic process • DNA replication • DNA repair • deoxyribonucleoside monophosphate biosynthetic process • nucleotide biosynthetic process • phosphoinositide-mediated signaling
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7298	22171
Ensembl	ENSG00000176890	ENSMUSG00000025747
UniProt	P04818	Q544L2
RefSeq	NM_001071 (mRNA)	NM_021288 (mRNA)
	NP_001062 (protein)	NP_067263 (protein)
Location	Chr 18: 0.65 - 0.66 Mb	Chr 5: 30.39 - 30.4 Mb
PubMed search	[1]	[2]

Thymidylate synthetase (EC 2.1.1.45)^[1] 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 synthetase can be inhibited by the thymidylate synthase inhibitors such as fluorinated pyrimidine fluorouracil, or certain folate analogues, including most notably raltitrexed (trade name Tomudex).

See also

• Pyrimidine analogues

References

Further reading

v • d • e PDB Gallery 1hvy: Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation   1hw3: STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS   1hw4: STRUCTURE OF THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS   1hzw: CRYSTAL STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE   1i00: CRYSTAL STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE, TERNARY COMPLEX WITH DUMP AND TOMUDEX   1ju6: Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate   1juj: Human Thymidylate Synthase Bound to dUMP and LY231514, a Pyrrolo(2,3-d)pyrimidine-based Antifolate   1ypv: Structure of human thymidylate synthase at low salt conditions   2onb: Human Thymidylate Synthase at low salt conditions with PDPA bound

External links

• MeSH Thymidylate+synthetase

This article on a gene on chromosome 18 is a stub. You can help Wikipedia by expanding it. v • d • e