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）： 双功能含镍酶，一氧化碳脱氢酶/乙酰辅酶A合酶（CODH/ACS），催化产乙酸生物体中二氧化碳（CO2）还原为一氧化碳（CO）以及从CO组装乙酰辅酶A。后一个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）物质的中间作用，并且对于生物圈中的自养碳固定过程很重要。最近对 CODH/ACS 酶的晶体结构测定揭示了 ACS 活性位点中的四配位四面体 Ni 原子。然而，四面体 Ni-(烷基) 和 Ni-(酰基) 复合物在配位化学中没有先例，并且该酶利用此类中心进行乙酰辅酶A组装的建议仍然存在争议。该提案的目标是通过使用由“连接的”三（吡唑基）硼酸酯配体系统支持的模型复合物来解决四面体 Ni 中心在 ACS 催化反应序列中的作用。这里提出的“连接的”三(吡唑基)硼酸酯配体具有模拟ACS活性位点中Ni中心的四面体几何形状和提供与乙酰辅酶A组装相关的可分离的有机金属Ni物种所必需的属性。提出了有机金属 Ni 模型配合物与相关生物底物的反应性研究，这将描绘 ACS 活性位点和催化功能中四面体 Ni 中心可用的潜在反应模式。