Steve Ealick's Research Group

Abstract:

Soriano EV, Clark VC, and Ealick SE. Structures of Human Deoxycytidine Kinase Product Complexes. Acta Crystallogr. D 63:1201-1207 (2007).

Human deoxycytidine kinase (dCK) is involved in the nucleotide biosynthesis salvage pathway and has also been shown to phosphorylate several anti-tumor and anti-viral prodrugs.  The structures of dCK alone and the dead end complex of dCK with substrate nucleoside and product ADP or UDP were previously reported (Godsey et al., 2006; Sabini et al., 2007; Sabini et al., 2003; Sabini et al., 2007; Zhang et al., 2006); however, there is currently no structure for a substrate or product complex.  Here we report dCK complexes with products dCMP, UDP and Mg2+ ion and with dAMP, UDP and Mg2+ ion.  Structural comparisons show that the product complexes with UDP and a dead end complex with substrate and UDP have similar active site conformations.