Thymidylate synthase/dCMP hydroxymethylase superfamily (IPR036926)
Short name: Thymidate_synth/dCMP_Mease_sf
- Thymidylate synthase (IPR000398)
- Bifunctional dihydrofolate reductase/thymidylate synthase (IPR012262)
- Deoxycytidylate hydroxymethylase (IPR014619)
- Thymidylate synthase, archaea (IPR014620)
- Thymidylate synthase/dCMP hydroxymethylase domain (IPR023451)
Thymidylate synthase (EC:188.8.131.52) [PMID: 6996564, PMID: 2117882]
catalyzes the reductive methylation
of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate
Thymidylate synthase also acts as a regulator of its own expression by binding and inactivating its own RNA. Due to its key role in the de novo pathway for thymidylate synthesis and, hence, DNA synthesis, it is one of the most conserved enzymes across species and phyla [PMID: 16162288,PMID: 16511011]. Thymidylate synthase is a well-recognized target for anticancer chemotherapy, as well as a valuable new target against infectious diseases [PMID: 16178783]. Interestingly, in several protozoa, a single polypeptide chain codes for both dihydrofolate reductase (DHFR) and thymidylate synthase (TS), forming a bifunctional enzyme (DHFR-TS), possibly through gene fusion at a single evolutionary point. DHFR-TS is also active as a dimer [PMID: 14555647].
This entry also includes dUMP hydroxymethylases and dCMP hydroxymethyltransferases from bacteriophages. dCMP-HMase catalyzes the reversible conversion of dCMP and CH2THF to hydroxymethyl-dCMP and THF. dUMP hydroxymethylase is encoded by several bacteriophages that infect Bacillus subtilis and contain hydroxymethyl-dUMP instead of dTMP in their DNA, for their own protection against the host restriction system [PMID: 10064578].
dCMP hydroxymethyltransferase has a subunit fold and a dimerization pattern in common with thymidylate synthases [PMID: 10064578].