Variations of the 2-His-1-carboxylate theme in mononudear non-heme FeIII oxygenases
Variations of the 2-His-1-carboxylate theme in mononudear non-heme FeIII oxygenases
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DOI：
10.1002/cbic.200600152
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发表时间：
2006-10-01
期刊：
影响因子：
3.2
通讯作者：
Nidetzky, B.
中科院分区：
文献类型：
--
作者：
Straganz, G. D.;Nidetzky, B.
两个组氨酸侧链和一个天冬氨酸或谷氨酸侧链的面部，三人组形成的典型金属配位基序在各种单核非血红素Fe II酶的催化中心。虽然这些活性位点是基于完全不相关的蛋白质折叠，并带来了广泛的化学转化，他们中的大多数人都有能力耦合双氧还原与有机底物的氧化。随着越来越多的蛋白质结构的解决，它已经变得很清楚，2-组氨酸-1-羧酸签名是一个范例的非血红素铁-II活性位点比长期以来一直认为，它可以被替代金属中心在各种加氧酶，结构与功能的关系和建议的催化机制进行了审查。通过三个组氨酸和一个谷氨酸的金属配位构成了cupin蛋白超家族的酶成员所描述的经典基序，例如酸-还原酮双加氧酶和槲皮素双加氧酶，其多种金属形式（包括Fe-II型）在自然界中被发现。半胱氨酸双加氧酶和二酮双加氧酶是基于cupin折叠的严格依赖于Fe-II的加氧酶，它们通过组氨酸的同源三联体结合催化金属，但缺乏第四个谷氨酸配体。α-酮戊二酸依赖性Fe-II卤化酶显示通过两个组氨酸作为唯一的蛋白质衍生配体的金属配位，而来自不同蛋白质折叠家族的胡萝卜素含氧糖的特征在于由四个组氨酸侧链组成的Fe-II位点。这些最近发现的双中心相对于它们的金属结合性能和反应坐标的O-2-依赖的转换，它们催化进行了讨论。
A facial, triad of two histidine side chains and one aspartate or glutamate side chain forms the canonical metal-coordinating motif in the catalytic centers of various mononuclear non-heme FeII enzymes. Although these active sites are based on totally unrelated protein folds and bring about a wide range of chemical transformations, most of them share the ability to couple dioxygen reduction with the oxygenation of an organic substrate. With the increasing number of protein structures now solved, it has become clear that the 2-His-1-carboxylate signature is less of a paradigm for non-heme Fe-II active sites than had long been thought and that it can be replaced by alternative metal centers in various oxygenases, the structure-function relationships and proposed catalytic mechanisms of which are reviewed here. Metal coordination through three histidines and one glutamate constitutes the classical motif described for enzyme members of the cupin protein superfamily, such as aci-reductone dioxygenase and quercetin dioxygenase, multiple metal forms of which (including the Fe-II type) are found in nature. Cysteine dioxygenase and diketone dioxygenase, which are strictly Fe-II-dependent oxygenases based on the cupin fold, bind the catalytic metal through the homologous triad of histidines, but lack the fourth glutamate ligand. An a-ketoglutarate-dependent Fe-II halogenase shows metal coordination by two histidines as the only protein-derived ligands, whilst carotene oxygenose, from a different protein fold family, features an Fe-II site consisting of four histidine side chains. These recently discovered metallocenters are discussed with respect to their metal-binding properties and the reaction coordinates of the O-2-dependent conversions they catalyze.