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Thymidylate synthase (EC 2.1.1.45) [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.

December 2004 / Pattern and text revised.

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

THYMIDYLATE_SYNTHASE, PS00091; Thymidylate synthase active site  (PATTERN)

Consensus pattern: R-x(2)-[LIVMT]-x(2,3)-[FWY]-[QNYDI]-x(8,13)-[LVESI]-x-P-C-[HAVMLC]-x(3)-[QMTLHD]-[FYWL]-x(0,1)-[LV] C is the active site residue Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00091 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00091 • Scan Swiss-Prot/TrEMBL entries against PS00091 • view ligand binding statistics

Matching PDB structures: 1AIQ 1AJM 1AN5 1AOB ... [ALL]

1	Authors	Benkovic S.J.
	Title	On the mechanism of action of folate- and biopterin-requiring enzymes.
	Source	Annu. Rev. Biochem. 49:227-251(1980).
	PubMed ID	6996564
	DOI	10.1146/annurev.bi.49.070180.001303

2	Authors	Ross P., O'Gara F., Condon S.
	Title	Cloning and characterization of the thymidylate synthase gene from Lactococcus lactis subsp. lactis.
	Source	Appl. Environ. Microbiol. 56:2156-2163(1990).
	PubMed ID	2117882

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