Thymidylate Synthase (Concentrate)

Thymidylate synthase (TS) is a key enzyme in the synthesis of DNA. TS, along with methyl donor 5,10-methylenetetrahydrofolate, catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) to generate the thymine nucleotides necessary for DNA biosynthesis. TS is also a target for fluorinated pyrimidine drugs such as 5-fluorouracil (5-FU). The active metabolite of 5-FU, FdUMP, competes with dUMP for the active binding site on the TS enzyme. FdUMP forms a ternary complex with TS and 5,10-methylenetetrahydrofolate, thereby inhibiting the enzyme.