5-FdUMP-Thymidylate Synthase complex

Thymidylate synthase is a key enzyme in nucleotide biosynthesis, catalyzing the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), providing the only de novo source of thymidylate for DNA synthesis in human cells[2][4][5]. The "5-FdUMP-Thymidylate Synthase complex" refers to the stable, covalent ternary complex formed when 5-FdUMP (an active metabolite of 5-FU and FUdR) binds irreversibly to the active site of thymidylate synthase in conjunction with the folate cofactor, resulting in potent and persistent enzyme inhibition, thereby blocking DNA synthesis and inducing cell death in rapidly dividing tumor cells[1][3][4][7].

Other names

Thymidylate synthetaseTSEC 2.1.1.45

Suicide inhibition of thymidylate synthase, leading to irreversible inhibition of dTMP (deoxythymidine monophosphate) synthesis, causing "thymineless death" of proliferating cells. Incorporation of fluorinated nucleotide analogs into DNA (when inhibition is incomplete or alternative metabolic pathways are engaged).