Analysis of zinc binding sites in protein crystal structures
Analysis of zinc binding sites in protein crystal structures
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DOI：
10.1002/pro.5560070805
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发表时间：
1998-08-01
期刊：
影响因子：
8
通讯作者：
Wodak, SJ
中科院分区：
文献类型：
--
作者：
Alberts, IL;Nadassy, K;Wodak, SJ
对蛋白质数据库中存放的高质量蛋白质晶体结构数据集中锌结合位点的几何特性进行了检查，以确定直接参与催化的锌位点和发挥结构作用的锌位点之间的重要差异。将锌主配位球中的配位角与每种配位几何形状的理想值进行比较，并将锌配位距离与剑桥结构数据库中的小型锌配合物中的配位距离进行比较，作为预期趋势的指南。我们发现主协调球中的距离和角度通常接近预期（或理想）值。偏差主要发生在氧配位原子上，并且被发现主要是由于氧配位配体与蛋白质残基的氢键、双齿结合排列和多锌位点造成的。我们发现，含氧残基（或水）与锌猎犬组氨酸的氢键在我们的数据集中几乎是普遍存在的，并定义了 elec-His-Zn 基序。立体化学分析表明，羧基电-His-Zn 基序在几何上是刚性的，而水电-His-Zn 基序表现出最大的几何变化。由于催化基序比结构基序具有更高比例的羧基电子原子，因此它们为锌结合提供了更刚性的框架。这在生物学上是可以理解的，因为酶中锌位置的微小扭曲会对酶促反应产生严重后果。我们还分析了提供电子的锌配体和残基的序列模式，并鉴定了内肽酶中的保守疏水残基，这些残基似乎也有助于稳定催化锌位点。蛋白质晶体结构中的锌结合模板源自这些观察。
The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. Ne find that H-bonding of oxygen containing residues (or water) to zinc hound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.