Control of thiolate nucleophilicity and specificity in zinc metalloproteins by hydrogen bonding: lessons from model compound studies.
Control of thiolate nucleophilicity and specificity in zinc metalloproteins by hydrogen bonding: lessons from model compound studies.
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通过氢键控制锌金属蛋白中硫醇盐的亲核性和特异性：模型化合物研究的教训。
DOI：
10.1021/ja029418i
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发表时间：
2003
影响因子：
15
通讯作者：
C. Carrano
中科院分区：
文献类型：
--
作者：
J. N. Smith;Z. Shirin;C. Carrano
一个单一的氢键之间的酰胺N-H和硫醇盐的硫在模型配合物中，旨在模拟锌硫醇盐蛋白质的结合位点，显示出减少的反应性的硫醇盐对亲电体高达2个数量级。此外，单个这样的键也足以实现强的（因此固有地不加选择的）烷基化剂如三甲基氧鎓四氟硼酸盐与二硫醇盐构建体中的单个硫之间的反应的接近100%的区域特异性。这些结果的重要性，在了解如何两个系统，如锌指的加塔家庭和大肠杆菌DNA修复蛋白Ada共享相同的pseudotetrahedral结构和tetrascysteinyl连接周围的锌可以实现这样广泛不同的（结构与反应）的作用，以及如何在多硫醇盐的系统中的反应特异性可以实现讨论。
A single hydrogen bond between an amide N-H and a thiolate sulfur in model complexes designed to mimic the binding site of zinc thiolate proteins, is shown to reduce the reactivity of the thiolate toward electrophiles by up to 2 orders of magnitude. In addition a single such bond is also sufficient to achieve nearly 100% regiospecificity of reaction between a strong, and hence inherently indiscriminate, alkylating agent like trimethyl oxonium tetrafluoroborate and a single sulfur in a dithiolate construct. The importance of these results in understanding how two systems such as the zinc fingers of the GATA family and the Escherichia coli DNA repair protein Ada which share the same pseudotetrahedral structure and tetrascysteinyl ligation around the zinc can fulfill such widely divergent (structural vs reactive) roles and how specificity of reaction in multithiolate-containing systems can be achieved is discussed.