Mechanistic diversity in a metalloenzyme superfamily
Mechanistic diversity in a metalloenzyme superfamily
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DOI：
10.1021/bi001814v
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发表时间：
2000-11-14
期刊：
影响因子：
2.9
通讯作者：
Armstrong, RN
中科院分区：
文献类型：
--
作者：
Armstrong, RN
现在人们意识到，蛋白质超家族中蛋白质，特别是酶的关系不仅可以通过它们的序列相似性和三维结构来理解，而且还可以通过与它们的功能属性相关的化学线索来理解。超家族成员之间的机械联系通常可以追溯到被催化的反应的限速步骤的共同过渡状态。本文分析了一个金属酶超家族，其成员催化了一系列不同的反应，这些反应具有无关的过渡态，但具有更一般的共同机理要求。邻位氧络合物(VOC)超家族是由具有成对的β-α-β基序的结构相关蛋白组成的，它提供了一个金属配位环境，具有两个或三个开放的或容易接近的配位位点，以促进金属离子在催化中的直接亲电参与。已知的被催化的反应类型包括异构化(乙草酸酶I)、差向异构化(甲基丙二酰辅酶A差向异构酶)、C-C键的氧化断裂(外加氧合酶)和亲核取代(磷霉素抗性蛋白)。VOC超家族提供的对机构空间的非凡访问似乎来自于一个简单的、伪对称的结构折叠，该折叠最大化了金属中心的催化多功能性。
It is now appreciated that the relationships of proteins, particularly enzymes, within a protein superfamily can be understood not only in terms of their sequence similarities and three-dimensional structures but also by chemical threads that relate their functional attributes. The mechanistic ties among superfamily members can often be traced to a common transition state for the rate-limiting step of the reactions being catalyzed. This paper presents an analysis of a metalloenzyme superfamily, the members of which catalyze a very diverse set of reactions with unrelated transition states but a more general common mechanistic imperative. The vicinal oxygen chelate (VOC) superfamily is composed of structurally related proteins with paired beta alpha beta beta beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis. The known types of reactions that are catalyzed include isomerizations (glyoxalase I), epimerizations (methylmalonyl-CoA epimerase), oxidative cleavage of C-C bonds (extradiol dioxygenase), and nucleophilic substitutions (fosfomycin resistance proteins). The remarkable access to mechanism space that is provided by the VOC superfamily appears to derive from a simple, pseudosymmetric structural fold that maximizes the catalytic versatility of the metal center.