Tetrahedral Ni Complexes as Acetyl-CoA Synthase Models

作为乙酰辅酶A合酶模型的四面体镍配合物

• 批准号: 6936738
• 负责人: JOSHUA S FIGUEROA
• 金额: $ 4.21万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-27 至 2007-06-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936738
• 关键词: X ray crystallography; acetyl coA; active sites; aldehyde /ketone oxidoreductase; alkyl group; carbon monoxide; catalyst; chemical reaction; chemical stability; chemical structure function; chemical synthesis; enzyme complex; enzyme model; enzyme substrate; ligands; organometallic compounds; oxidation reduction reaction; postdoctoral investigator

DESCRIPTION (provided by applicant): The bifunctional nickel-containing enzyme, carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS), catalyzes the reduction of carbon dioxide (CO2) to carbon monoxide (CO) and the assembly of acetyl-CoA from CO in acetogenic organisms. The latter reaction is a rare example of a biological organometallic reaction sequence in which the intermediacy of Ni-(alkyl) and Ni-(acyl) species are proposed and is important to autotropic carbon-fixation processes in the biosphere. Recent crystallographic structure determinations of a CODH/ACS enzyme have revealed - what appears to be - a four-coordinate, tetrahedral Ni atom in the ACS active site. However, tetrahedral Ni-(alkyl) and Ni-(acyl) complexes have no precedent in coordination chemistry and the suggestion that the enzyme utilizes such centers for acetyl-CoA assembly remains controversial. The goal of this proposal is to address the role of tetrahedral Ni centers in the reaction sequences of ACS catalysis through the use of model complexes supported by a "linked" tris(pyrazolyl)borate ligand system. The "linked" tris(pyrazolyl)borate ligands proposed here possess the attributes necessary to mimic the tetrahedral geometry of the Ni centers in the ACS active site and to provide isolable organometallic Ni species relevant to acetyl-CoA assembly. Reactivity studies of the organometallic Ni model complexes with relevant biological substrates are proposed which will delineate potential reactivity patterns available to the tetrahedral Ni center in the ACS active site and catalytic function.

描述（由申请人提供）： 含镍酶，一氧化碳脱氢酶/乙酰-COA合酶（CODH/ACS）催化二氧化碳（CO2）的碳二氧化碳（CO）和乙酰基生物体中CO的乙酰辅酶A组装的碳二氧化碳（CO2）的还原。后一种反应是生物有机金属反应序列的罕见例子，其中提出了Ni-（烷基）和NI-（酰基）物种的中间体，对生物圈中的自发碳固定过程很重要。 CODH/ACS酶的最新晶体结构测定已揭示了ACS活性位点中的四个坐标四面体Ni原子。然而，四面体ni-（烷基）和ni-（酰基）复合物在协调化学方面没有先例，并且建议该酶利用此类中心用于乙酰-COA组装仍然有争议。该提案的目的是通过使用由“链接” Tris（吡唑基）硼酸盐配体系统支持的模型复合物来解决四面体NI中心在ACS催化的反应序列中的作用。这里提出的“链接” Tris（吡唑基）硼酸盐配体具有模仿ACS活性位点NI中心的四面体几何形状所需的属性，并提供与乙酰基-COA组装相关的可隔离有机金属物种。提出了与相关生物底物的有机金属Ni模型复合物的反应性研究，该复合物将描述ACS主动位点和催化功能的四面体NI中心可用的潜在反应性模式。