Structures of human deoxycytidine kinase product complexes

Abstract

Human deoxycytidine kinase (dCK) is involved in the nucleotide-biosynthesis salvage pathway and has also been shown to phosphorylate several antitumor and antiviral prodrugs. The structures of dCK alone and the dead-end complex of dCK with substrate nucleoside and product ADP or UDP have previously been reported; however, there is currently no structure available for a substrate or product complex. Here, the structures of dCK complexes with the products dCMP, UDP and Mg2+ ion, and with dAMP, UDP and Mg2+ ion are reported. Structural comparisons show that the product complexes with UDP and a dead-end complex with substrate and UDP have similar active-site conformations.