Thymidylate synthase (EC:184.108.40.206) [PMID: 6996564, PMID: 2117882]
catalyzes the reductive methylation
of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
This provides the sole de novo pathway for
production of dTMP and is the only enzyme in folate metabolism in which the
5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer [PMID: 3099389].
The enzyme is essential for regulating the balanced supply of the 4 DNA
precursors in normal DNA replication: defects in the enzyme activity
affecting the regulation process cause various biological and genetic
abnormalities, such as thymineless death [PMID: 2243092]. The enzyme 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 [PMID: 3099389].
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.
This entry also contains some dCMP hydroxymethyltransferases EC:220.127.116.11.