Structures of human deoxycytidine kinase product complexes.
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.
Soriano
Erika V
EV
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
Clark
Valerie C
VC
Ealick
Steven E
SE
D018360:Crystallography, X-Ray; D003842:Deoxycytidine Kinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003843:Deoxycytidine Monophosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014530:Uridine Diphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D003843:Deoxycytidine Monophosphate; D014530:Uridine Diphosphate; D003842:Deoxycytidine Kinase