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How does binuclear zinc amidohydrolase FwdA work in the initial step of methanogenesis: From formate to formyl-methanofuran
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2018-05-11 , DOI: 10.1016/j.jinorgbio.2018.05.004
Xue-Wei Zhang , Shi-Lu Chen

The initial step of methanogenesis is the fixation of CO2 to formyl-methanofuran (formyl-MFR) catalyzed by formyl-MFR dehydrogenase, which can be divided into two half reactions. Herein, the second half reaction catalyzed by FwdA (formyl-methanofuran dehydrogenase subunit A), i.e., from formate to formyl-methanofuran, has been investigated using density functional theory and a chemical model based on the X-ray crystal structure. The calculations indicate that, compared with other well-known di-zinc hydrolases, the FwdA reaction employs a reverse mechanism, including the nucleophilic attack of MFR amine on formate carbon leading to a tetrahedral gem-diolate intermediate, two steps of proton transfer from amine to formate moieties assisted by the Asp385, and the CO bond dissociation to form the formyl-MFR product. The second step of proton transfer from the amine moiety to the Asp385 is rate-limiting with an overall barrier of 21.2 kcal/mol. The two zinc ions play an important role in stabilizing the transition states and intermediates, in particular the negative charge at the formate moiety originated from the nucleophilic attack of the MFR amine. The work here appends a crucial piece in the methanogenic mechanistics and advances the understanding of the global carbon cycle.



中文翻译:

双核锌酰胺水解酶FwdA在甲烷生成的初始阶段如何工作:从甲酸盐到甲酰-甲呋喃

甲烷生成的第一步是将甲酰-MFR脱氢酶催化将CO 2固定在甲酰-甲呋喃(甲酰-MFR)上,该过程可分为两个半反应。在本文中,已经使用密度泛函理论和基于X射线晶体结构的化学模型研究了由FwdA(甲酰基-甲基呋喃脱氢酶亚基A)催化的后半反应,即从甲酸酯到甲酰基-甲基呋喃。计算表明,与其他知名的二锌水解酶相比,FwdA反应采用了相反的机制,包括MFR胺对甲酸碳的亲核攻击,导致四面体宝石-二醇酸酯中间体,质子从胺转移的两个步骤在Asp385和C的帮助下形成部分O键解离形成甲酰基-MFR产物。质子从胺部分转移到Asp385的第二步是限速的,总势垒为21.2 kcal / mol。这两个锌离子在稳定过渡态和中间体方面起着重要作用,尤其是在甲酸部分的负电荷源于MFR胺的亲核攻击。此处的工作是甲烷生成机理的重要组成部分,并增进了对全球碳循环的理解。

更新日期:2018-05-11
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