Region Directed Mutagenesis of Varicella-Zoster Virus Thymidylate Synthase

[摘要] Thymidylate synthase (TS) catalyses the reductive methylation of deoxyuridine monophosphate by 5,10-methylenetetrahydrofolate to produce thymidylate and dihydrofolate. In the reaction the enzyme is present initially as an open complex that closes down progressively as ligands bind. The binary complex which is formed as the substrate dUMP binds has an active site that is open and structurally very close to the unliganded state. It is upon binding of the folate cofactor that structural changes occur and the enzyme forms a closed ternary structure. In contrast to the movements of large domains seen in other proteins upon ligand binding, the changes in TS involves segmental accommodation in which segments of secondary structural elements all move in concert towards the active site. The two largest shifts involve the C-terminus and DRTG loop which moves 4A to close over the active site.

[发布机构] University:University of Glasgow

[关键词] Virology, Biochemistry