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科研人员发现配体场反转可调控生物有机金属的反应活性
作者:小柯机器人 发布时间:2021/1/14 15:58:20

美国俄亥俄州立大学Hannah S. Shafaat团队利用光谱学和计算研究了乙酰辅酶A合成酶的生化模型,发现配体场反转可以作为控制生物有机金属反应活性的机制。该研究于2021年1月8日发表于《美国化学会志》。

据了解,生物全球碳循环主要是通过微生物镍酶的调节,包括一氧化碳脱氢酶(CODH),乙酰辅酶A合成酶(ACS)和甲基辅酶M还原酶(MCR)。这些体系被认为通过催化过程中有机金属中间体,然而对这些物质的表征仍然具有挑战性。

课题组人员已经建立了一个镍取代天青蛋白,基于该结构开发基于蛋白的酶中间体模型,包括ACS的有机金属态。

在这项工作中,研究组使用脉冲EPR光谱和计算手段,报告了对S=1/2的Ni–CO以及Ni–CH3态的全面研究。尽管Ni-CO态显示出常规的金属-配体相互作用和经典的配体场,但甲基质子和镍之间的Ni-CH3超精细相互作用表明距离比阴离子甲基配体所期望的距离更近。

相反,结构分析表明近平面甲基配体可以最好被描述为阳离子。与这一结论一致,Ni–CH3物种的前沿分子轨道显示一个以配体为中心的LUMO,在金属中心具有d9种群,而不是通过氧化加成生成的典型金属-烷基物质的d7种群。

总体而言,这些数据支持存在Ni-CH3 Az物种的反向配体场构型,其中最低的空轨道以配体为中心,而不是带正电的金属。这些分析提供了在生物体系中存在反转配体场的第一个证据。科研人员在非变性ACS蛋白的情境下讨论了Ni–CO以及Ni–CH3物种的电子结构的功能相关性,并提出反转配体场是调控ACS以及其他含巯基金属酶反应活性的机制。

附:英文原文

Title: Ligand Field Inversion as a Mechanism to Gate Bioorganometallic Reactivity: Investigating a Biochemical Model of Acetyl CoA Synthase Using Spectroscopy and Computation

Author: Effie C. Kisgeropoulos, Anastasia C. Manesis, Hannah S. Shafaat

Issue&Volume: January 8, 2021

Abstract: The biological global carbon cycle is largely regulated through microbial nickel enzymes, including carbon monoxide dehydrogenase (CODH), acetyl coenzyme A synthase (ACS), and methyl coenzyme M reductase (MCR). These systems are suggested to utilize organometallic intermediates during catalysis, though characterization of these species has remained challenging. We have established a mutant of nickel-substituted azurin as a scaffold upon which to develop protein-based models of enzymatic intermediates, including the organometallic states of ACS. In this work, we report the comprehensive investigation of the S = 1/2 Ni–CO and Ni–CH3 states using pulsed EPR spectroscopy and computational techniques. While the Ni–CO state shows conventional metal–ligand interactions and a classical ligand field, the Ni–CH3 hyperfine interactions between the methyl protons and the nickel indicate a closer distance than would be expected for an anionic methyl ligand. Structural analysis instead suggests a near-planar methyl ligand that can be best described as cationic. Consistent with this conclusion, the frontier molecular orbitals of the Ni–CH3 species indicate a ligand-centered LUMO, with a d9 population on the metal center, rather than the d7 population expected for a typical metal–alkyl species generated by oxidative addition. Collectively, these data support the presence of an inverted ligand field configuration for the Ni–CH3 Az species, in which the lowest unoccupied orbital is centered on the ligands rather than the more electropositive metal. These analyses provide the first evidence for an inverted ligand field within a biological system. The functional relevance of the electronic structures of both the Ni–CO and Ni–CH3 species are discussed in the context of native ACS, and an inverted ligand field is proposed as a mechanism by which to gate reactivity both within ACS and in other thiolate-containing metalloenzymes.

DOI: 10.1021/jacs.0c10135

Source: https://pubs.acs.org/doi/10.1021/jacs.0c10135

 

期刊信息

JACS:《美国化学会志》,创刊于1879年。隶属于美国化学会,最新IF:14.612
官方网址:https://pubs.acs.org/journal/jacsat
投稿链接:https://acsparagonplus.acs.org/psweb/loginForm?code=1000