PROSITE documentation PDOC00086 [for PROSITE entry PS00091]
Thymidylate synthase active site


Thymidylate synthase (EC [1,2] catalyzes the reductive methylation of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate to dihydrofolate. Thymidylate synthase plays an essential role in DNA synthesis and is an important target for certain chemotherapeutic drugs.

Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain.

A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

THYMIDYLATE_SYNTHASE, PS00091; Thymidylate synthase active site  (PATTERN)


1AuthorsBenkovic S.J.
TitleOn the mechanism of action of folate- and biopterin-requiring enzymes.
SourceAnnu. Rev. Biochem. 49:227-251(1980).
PubMed ID6996564

2AuthorsRoss P. O'Gara F. Condon S.
TitleCloning and characterization of the thymidylate synthase gene from Lactococcus lactis subsp. lactis.
SourceAppl. Environ. Microbiol. 56:2156-2163(1990).
PubMed ID2117882

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