Insights into the Mechanism of Aromatic Ring Cleavage of Noncatecholic Compound 2-Aminophenol by Aminophenol Dioxygenase: A Quantum Mechanics/Molecular Mechanics Study
Insights into the Mechanism of Aromatic Ring Cleavage of Noncatecholic Compound 2-Aminophenol by Aminophenol Dioxygenase: A Quantum Mechanics/Molecular Mechanics Study
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DOI：
10.1021/acscatal.6b00372
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发表时间：
2016-06-01
期刊：
影响因子：
12.9
通讯作者：
Lai, Wenzhen
中科院分区：
文献类型：
--
作者：
Dong, Geng;Lu, Jiarui;Lai, Wenzhen
2-氨基酚1，6-双加氧酶（APD）是一种二醇外双加氧酶，负责2-氨基酚（2AP）羟基邻位的开环反应。为了阐明反应机理，我们进行了量子力学/分子力学（QM/ MM）计算。的基板（单齿或双齿）的铁中心的结合模式被发现有一个至关重要的作用，在双氧活化。Fe-O-2与2AP双齿键合的加合物具有五重基态，具有Fe-III-superoxo特征，而Fe-O-2与单齿键合的底物的加合物的特征在于底物自由基-Fe-II-超氧化物。与其他extradiol双加氧酶，使用的Fe-O-2加合物的superoxo部分来攻击的基板，儿茶酚类似物裂解，我们发现这里的Fe-II-O（H）O中间体形成通过两个连续的质子耦合电子转移步骤从最初的Fe-III-superoxo物种是负责的攻击。重要的是，第二球His 195残基作为酸碱催化剂介导质子转移（与电子转移相关）。本文的研究拓展了我们对extradiol双加氧酶的理解，特别是那些催化非儿茶酚底物环裂解的酶。
2-Aminophenol 1,6-dioxygenase (APD) is an extradiol dioxygenase responsible for the ring cleavage of 2aminophenol (2AP) at the position ortho to the hydroxyl substituent. To elucidate the reaction mechanism, we conducted quantum mechanical/molecular mechanical (QM/ MM) calculations. The mode of binding of the substrate (monodentate or bidentate) to the iron center was found to have a crucial role in dioxygen activation. The Fe-O-2 adducts with 2AP bound bidentately has a quintet ground state having a Fe-III-superoxo character, while the Fe-O-2 adducts with a monodentately bound substrate has been characterized as a substrate radical-Fe-II-superoxide. Unlike other extradiol dioxygenases that cleave catechol analogues using the superoxo moiety of the Fe-O-2 adducts to attack the substrate, we found here an Fe-II-O(H)O intermediate formed through two sequential proton-coupled electron transfer steps from the initial Fe-III-superoxo species is responsible for the attack. Importantly, the second-sphere His195 residue acts as an acid base catalyst to mediate proton transfer (associated with electron transfer). The study presented here expands our understanding of the extradiol dioxygenases, especially those catalyzing the ring cleavage of noncatecholic substrates.