Nucleoside monophosphate kinases: Structure, mechanism, and substrate specificity
Nucleoside monophosphate kinases: Structure, mechanism, and substrate specificity
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DOI：
10.1002/9780470123195.ch4
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Tsai, MD
中科院分区：
文献类型：
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作者：
Yan, HG;Tsai, MD
从动力学和结构方面综述了近年来腺苷酸激酶、鸟苷酸激酶、尿苷酸激酶和胞苷酸激酶的催化机理。所有四种激酶都有一个高度相关的三级结构，其特征是中央五链平行β -片，两侧有螺旋，以及被指定为CORE， NMPbind和LID结构域的三个区域。通过反复的结构-功能研究，催化机制继续被完善到更高的分辨率，并且在腺苷酸激酶的情况下，位点定向诱变的优势和局限性得到了很好的说明。活性位点残基的身份和作用现在似乎得到了解决，这篇综述描述了如何用非天然氨基酸侧链取代特定位点已被证明是一个重大进展。同样，有越来越多的证据表明，基于(a)磷基转移的立体化学过程，(b)几何考虑，(c)可能的电子分布的检查，(d)磷基受体相对于被转移的磷基的取向，(e)镁离子最可能的作用，(f)缺乏溶剂水的限制进入，以及(g)氧-18动力学同位素的结果，磷基转移是通过结合过渡态发生的。影响实验。
The catalytic mechanisms of adenylate kinase, guanylate kinase, uridylate kinase, and cytidylate kinase are reviewed in terms of kinetic and structural information that has been obtained in recent years. All four kinases share a highly related tertiary structure, characterized by a central five-stranded parallel beta-sheet with helices on both sides, as well as the three regions designated as the CORE, NMPbind, and LID domains. The catalytic mechanism continues to be refined to higher levels of resolution by iterative structure-function studies, and the strengths and limitations of site-directed mutagenesis are well illustrated in the case of adenylate kinase. The identity and roles of active site residues now appear to be resolved, and this review describes how specific site substitutions with unnatural amino acid side-chains have proven to be a major advance. Likewise, there is mounting evidence that phosphoryl transfer occurs by an associative transition state, based on (a) the stereochemical course of phosphoryl transfer,(b) geometric considerations,(c) examination of likely electronic distributions,(d) the orientation of the phosphoryl acceptor relative to the phosphoryl being transferred,(e) the most likely role of magnesium ion,(f) the lack of restricted access of solvent water, and (g) the results of oxygen-18 kinetic isotope. effect experiments.