Structural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues .

ABSTRACT: The physiological role of human deoxycytidine kinase (dCK) is to phosphorylate deoxynucleosides required for DNA synthesis, with the exception of thymidine. Previous structural analysis of dCK implicated steric factors, specifically the thymine methyl group at the 5-position, that prevent thymidine phosphorylation by dCK. This hypothesis is supported by the observation that mutations that enlarge the active site cavity in proximity to the nucleoside 5-position endow dCK with the ability to phosphorylate thymidine. However, in conflict with this hypothesis was our discovery that the cytidine analogue 5-methyldeoxycytidine (5-Me-dC), an isostere of thymidine, can indeed be phosphorylated by wild-type (WT) dCK. To reconcile this seemingly contradicting observation, and to better understand th

SUBMITTER: Hazra S 

PROVIDER: S-EPMC2925221 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature