Eriksson S, Munch-Petersen B, Johansson K, Eklund H
Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Biomedical Center, Uppsala.
Cell Mol Life Sci. 2002 Aug;59(8):1327-46. doi: 10.1007/s00018-002-8511-x.
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.
脱氧核糖核苷激酶可使脱氧核糖核苷磷酸化,这是通过补救途径生物合成DNA前体中的关键反应。它们在医学上的重要性源于它们能激活多种抗癌和抗病毒药物,如2-氯-2'-脱氧腺苷、叠氮胸苷和阿昔洛韦。在此,我们综述目前已知的每种哺乳动物激酶以及脱氧核糖核苷激酶家族的其他一些成员。先描述了这些酶的生化特性,接着概述了对该酶家族进行的结构研究,包括催化机制以及反馈抑制机制。展示了该家族中其他蛋白质的同源模型,最后描述了底物和底物类似物特异性的决定因素。