Quantum mechanics/molecular mechanics investigation of the mechanism of phosphate transfer in human uridine-cytidine kinase 2.

ABSTRACT: The mechanisms of enzyme-catalyzed phosphate transfer and hydrolysis reactions are of great interest due to their importance and abundance in biochemistry. The reaction may proceed in a stepwise fashion, with either a pentavalent phosphorane or a metaphosphate anion intermediate, or by a concerted SN2 mechanism. Despite much theoretical work focused on a few key enzymes, a consensus for the mechanism has not been reached, and examples of all three possibilities have been demonstrated. We have investigated the mechanism of human uridine-cytidine kinase 2 (UCK2, EC 2.7.1.48), which catalyzes the transfer of a phosphate group from ATP to the ribose 5'-hydroxyl of cytidine and uridine. UCK2 is normally expressed in human placenta, but is overexpressed in certain cancer cells, where it is respo

SUBMITTER: Smith AJ 

PROVIDER: S-EPMC3048851 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature