Theoretical study of the phosphotriesterase reaction mechanism
Theoretical study of the phosphotriesterase reaction mechanism
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DOI：
10.1021/jp068500n
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发表时间：
2007-02-15
影响因子：
3.3
通讯作者：
Himo, Fahmi
中科院分区：
文献类型：
--
作者：
Chen, Shi-Lu;Fang, Wei-Hai;Himo, Fahmi
磷酸三酯酶（PTE）是一种双核锌酶，催化剧毒有机磷酸三酯的水解。在本工作中，我们采用杂化密度泛函方法B3LYP研究了PTE的反应机理。我们提出了一个势能面的反应，并提供表征的过渡态和中间体。我们利用高分辨晶体结构构建了一个包含两个锌离子和它们的第一壳配体的PTE活性中心模型。计算结果为PTE水解磷酸三酯的缔合机理提供了有力的支持。没有质子化的离去基团被认为是必要的。特别是，计算表明，亲核性的桥接氢氧化物是足够的水解反应中使用，一个功能，这是一个重要的其他一些二锌酶。
Phosphotriesterase (PTE) is a binuclear zinc enzyme that catalyzes the hydrolysis of extremely toxic organophosphate triesters. In the present work, we have investigated the reaction mechanism of PTE using the hybrid density functional theory method B3LYP. We present a potential energy surface for the reaction and provide characterization of the transition states and intermediates. We used the high resolution crystal structure to construct a model of the active site of PTE, containing the two zinc ions and their first shell ligands. The calculations provide strong support to an associative mechanism for the hydrolysis of phosphotriesters by PTE. No protonation of the leaving group was found to be necessary. In particular, the calculations demonstrate that the nucleophilicity of the bridging hydroxide is sufficient to be utilized in the hydrolysis reaction, a feature that is of importance for a number of other di-zinc enzymes.