ABSTRACT
TS catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), with reduced folate 5,10-methylenetetrahydrofolate (CH2THF) as the methyl donor. is reaction provides the sole de novo source of thymidylate, which is necessary for DNA replication and repair. e 36-kDa TS protein is a dimer, both subunits of which contain a nucleotide-binding site and a binding site for
CH2THF. e 5-FU metabolite FdUMP binds to the nucleotide-binding site of TS, forming a stable ternary with the enzyme and CH2THF, thereby blocking binding of the normal substrate dUMP and inhibiting dTMP synthesis.
