CARBOXYLATE HISTIDINE ZINC INTERACTIONS IN PROTEIN-STRUCTURE AND FUNCTION
CARBOXYLATE HISTIDINE ZINC INTERACTIONS IN PROTEIN-STRUCTURE AND FUNCTION
复制标题
DOI：
10.1021/ja00198a065
复制
发表时间：
1989-08-02
影响因子：
15
通讯作者：
ALEXANDER, RS
中科院分区：
文献类型：
--
作者：
CHRISTIANSON, DW;ALEXANDER, RS
分析Brookhaven蛋白质数据库中所含蛋白质的三维结构中的结合金属离子。超过150种独特的蛋白质结构是可用的，其中包含七种不同类型的结合金属离子。铁、钙和锌是最常见的，生物锌的扩展配位多面体是本研究的主题。特别地，经常发现连接锌离子的组氨酸残基桥接锌离子和附近天冬氨酸（有时谷氨酸）残基的羧酸酯侧链。我们指的是间接的羧酸-金属协调的羧酸-组氨酸-锌的相互作用，我们观察到这一功能在所有锌酶的三维结构的报告。此外，我们还观察到相关的羰基组氨酸锌相互作用的一些金属蛋白。我们观察到一些直接的羧酸锌的相互作用，和他们的协调立体化学是专门的syn相对于羧酸。 基于可用的蛋白质结构及其已知的同系物，可以鉴定超过30个跨桥接组氨酸的间接羧酸盐-锌配位的实例。羧酸盐-组氨酸-锌三联体在许多含锌蛋白质和酶的功能中可能是重要的，例如，通过加强金属络合或调节锌结合水的亲核性。天然蛋白质中存在未复合的羧酸-组氨酸对（比单独的组氨酸碱性更强的基团）也可以发出调节金属结合位点的信号。实际上，丝氨酸蛋白酶活性位点的Asp-His对可能包含与锌蛋白酶金属配位多面体的Asp-His的结构进化联系。
The three-dimensional structures of proteins contained in the Brookhaven Protein Data Bank were analyzed for bound metal ions. Well over 150 unique protein structures are available which contain seven different types of bound metal ions. Iron, calcium, and zinc are most commonly observed, and the extended coordination polyhedra of biological zinc are the subject of this study. In particular, histidine residues ligating zinc ions are often found to bridge both the zinc ion and the carboxylate side chain of a nearby aspartate (sometimes glutamate) residue. We refer to the carboxylate-histidine-zinc interaction as indirect carboxylate-metal coordination, and we observe this feature in all zinc enzymes of reported three-dimensional structure. Additionally, we also observe a related carbonyl-histidine-zinc interaction in some metalloproteins. We observe some direct carboxylate-zinc interactions, and their coordination stereochemistry is exclusively syn with respect to the carboxylate. On the basis of available protein structures and known homologues thereof, more than 30 examples of indirect carboxylate-zinc coordination across bridging histidine can be identified. The carboxylate-histidine-zinc triad may be important in the function of many zinc-containing proteins and enzymes, e.g., by strengthening metal complexation or modulating the nucleophilicity of zinc-bound water. The presence of an uncomplexed carboxylate-histidine couple (a grouping more basic than histidine alone) in a native protein can also signal a regulatory metal binding site. Indeed, the Asp----His couple of the serine protease active site may comprise a structural, evolutionary link to the Asp----His of the zinc protease metal coordination polyhedron.