Abstract.
Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides, a crucial reaction in biosynthesis of DNA precursors through the salvage pathway. Their medical interest stems from their activation of a number of anticancer and antiviral drugs such as 2-chloro-2′-deoxyadenosine, azidothymidine and acyclovir. Here we review what is presently known about each of the mammalian kinases as well as some other members of the deoxyribonucleoside kinase family. A description of the biochemical properties of the enzymes is followed by an overview of the structural studies made on this family of enzymes, including the catalytic mechanism as well as the mechanism for feedback inhibition. A presentation of homology models of other proteins in the family is made and, finally, the determinants of substrate and substrate analog specificities are described.
Keywords: Key words. Deoxyribonuncleoside kinases; substrate specificity; phosphoryl transfer; nucleoside analogs; feedback inhibition; biochemical properties.
Footnotes
Received 8 February 2002; received after revision 21 March 2002; accepted 26 March 2002