Thymidylate synthase

Function

Thymidylate synthase (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair^[1]. In protozoa, dihydrofolate reductase (DHFR) and TS are expressed as a bifunctional monomeric enzyme (DHFR-TS) with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – ThyA and ThyX. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes.

Relevance

TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.^[2]

Structural highlights

TS ^[3]. Water molecules shown as red spheres.