Structural basis for substrate specificities of cellular deoxyribonucleoside kinases
Structural basis for substrate specificities of cellular deoxyribonucleoside kinases
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DOI：
10.1038/89661
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发表时间：
2001-07-01
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影响因子：
--
通讯作者：
Eklund, H
中科院分区：
文献类型：
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作者：
Johansson, K;Ramaswamy, S;Eklund, H
脱氧核糖核苷激酶使脱氧核糖核苷磷酸化并激活一些医学上重要的核苷类似物。本文报道了果蝇脱氧核糖核苷激酶与脱氧胞苷结合在核苷结合位点的结构，以及人脱氧鸟苷激酶与ATP结合在核苷底物结合位点的结构。与人类激酶相比，果蝇激酶具有更宽的底物间隙，这可能是该酶具有广泛底物特异性的原因。人脱氧鸟苷激酶对嘌呤底物具有高度特异性；这显然是由于Arg 118的存在，它与衬底提供了有利的氢键相互作用。这两个新的结构为细胞脱氧核糖核苷激酶的底物特异性提供了解释。
Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases.