A quantum chemical study of the catalysis for cytidine deaminase: Contribution of the extra water molecule
A quantum chemical study of the catalysis for cytidine deaminase: Contribution of the extra water molecule
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DOI：
10.1021/ci050479k
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发表时间：
2006-05-01
影响因子：
5.6
通讯作者：
Aida, Misako
中科院分区：
文献类型：
--
作者：
Matsubara, Toshiaki;Ishikura, Masashi;Aida, Misako
胞苷脱氨酶是一种重要的酶，负责胞苷的水解脱氨，这是将癌症药物前体转化为活体活性形式的关键步骤。在胞苷脱氨酶的间隙中，有水的胞苷有效地转化为有氨的尿苷。本文采用量子化学方法，以胞嘧啶为胞苷模型，以胞嘧啶为胞苷脱氨酶活性位点的模型分子，考察了胞苷脱氨酶对水解脱氨酶的催化作用。我们特别研究了溶剂中水分子对催化作用的贡献，因为晶体结构的x射线衍射分析揭示了在与裂口内活性位点结合的底物附近存在水分子。计算结果表明，溶剂中多余的水分子有可能支持胞苷脱氨酶的催化作用。
Cytidine deaminase is known as an important enzyme responsible for the hydrolytic deamination of cytidine, which is applied as a key step to the conversion of the precursor of the cancer drug to an active form in the living body. Cytidine with water is efficiently converted to uridine with ammonia in the cleft of cytidine deaminase. In this work, the catalysis of cytidine deaminase for the hydrolytic deamination was examined using cytosine as a model of cytidine and the model molecules for the active site of cytidine deaminase by means of the quantum chemical method. We especially investigated the contribution of the water molecule from the solvent to the catalysis, because the X-ray diffraction analysis of a crystal structure has revealed the existence of the water molecule in the vicinity of the substrate bound to the active site inside the cleft. Our computations showed that the extra water molecule from the solvent has a possibility to support the catalysis of cytidine deaminase.