Hydride Transfer versus Hydrogen Radical Transfer in Thymidylate Synthase

摘要

Thymidylate synthase (TS)(EC 2.1.1.45)catalyzes the last committed step in the de novo biosynthesis of 2'-deoxythymidine-5'-monophosphate (dTMP,one of the four building blocks of DNA).The enzyme catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP)to dTMP.Two independent reactions are involved in which the cofactor N~5,N~(10)-methylene-5,6,7,8-tetrahydrofolate (CH_2H_4folate)serves first as a donor of a methylene group and second as a donor of a hydride ion.