Advanced Spectroscopic and Computational Analysis of Metal Sites in Enzymes, Biomimetic Models, and Catalytic Intermediates.

酶、仿生模型和催化中间体中金属位点的高级光谱和计算分析。

• 批准号: 10674032
• 负责人: MICHAEL P HENDRICH
• 金额: $ 27.71万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674032
• 关键词: Active Sites; Affect; Amino Acids; Benchmarking; Biochemical; Biomimetics; Chemicals; Complex; Computer Analysis; Computing Methodologies; Databases; Disease; Elements; Ensure; Enzymes; Finding by Cause; Glean; Goals; Human; Hydrogen Bonding; Investigation; Joints; Kinetics; Life; Metalloproteins; Metals; Modeling; Molecular; Monitor; Organism; Proteins; Protocols documentation; Reaction; Research; Research Personnel; Site; Time; Work; metalloenzyme; millisecond; protein complex

Advanced Spectroscopic and Computational Analysis of Metal Sites in Enzymes, Biomimetic Models, and Catalytic Intermediates. Summary/Abstract Life of all organisms, including humans, depends on the activation of small stable molecules by metalloproteins to provide selective and rapid chemical transformations. The goal of the proposed research is to elucidate how specific metalloenzymes function by monitoring and analyzing the atomic level changes that occur at the metal active site during the reaction. These studies are augmented with benchmark studies of biomimetic complexes. The understanding gleaned from this work will provide a molecular basis for finding causes and remedies of diseases. The focus of the research efforts will be on how the interfacing of the active sites in metalloproteins with the protein matrix affects enzymatic function. The primary atomic coordination to the metal is of critical importance, but in many cases, weaker secondary sphere interactions, usually hydrogen bonds from nearby amino acid residues can have significant influence as well. The investigations in our lab use advanced spectroscopic and computational methods, providing detailed characterizations of the metal active sites in proteins that can be compared with an extensive database of benchmarks that we and other researchers have gathered from synthetic model complexes over the years. To understand how an enzyme works, we study key steps in their chemical mechanism by trapping and characterizing reactive intermediates and tracking their elemental kinetics on a millisecond time scale. The work is highly collaborative as we depend on the expertise of many synthetic and biochemical research groups to ensure access to biomimetic and protein complexes that can be, through joint effort, prepared cleanly with well-defined protocols.

酶中金属位点的高级光谱和计算分析，仿生模型， 催化中间体。 摘要/摘要 包括人类在内的所有生物体的生命都依赖于小的稳定分子的激活， 金属蛋白提供选择性和快速的化学转化。建议的目标 研究的目的是通过监测和分析金属酶的原子结构， 在反应过程中在金属活性部位发生的能级变化。这些研究增加了 仿生复合物的基准研究。从这项工作中获得的理解将提供一个 寻找病因和治疗疾病的分子基础。研究工作的重点将是 金属蛋白中活性位点与蛋白质基质的界面如何影响酶促反应 功能与金属的初级原子配位至关重要，但在许多情况下， 二级球相互作用，通常是来自附近氨基酸残基的氢键， 影响力也很大。我们实验室的研究使用了先进的光谱和计算技术， 方法，提供蛋白质中金属活性位点的详细表征， 利用我们和其他研究人员从合成材料中收集的大量基准数据库， 多年来的复杂模型。为了了解酶是如何工作的，我们研究了它们的关键步骤。 通过捕获和表征活性中间体并跟踪其元素的化学机理 毫秒级的动力学这项工作是高度协作的，因为我们依赖于 许多合成和生物化学研究小组，以确保获得仿生和蛋白质复合物 这可以通过共同努力，用明确定义的协议干净地准备好。

项目成果

The Mechanism of Formation of Active Fe-TAMLs Using HClO Enlightens Design for Maximizing Catalytic Activity at Environmentally Optimal, Circumneutral pH.

• DOI: 10.1021/acs.inorgchem.3c00104
• 发表时间: 2023-04-10
• 期刊: INORGANIC CHEMISTRY
• 影响因子: 4.6
• 作者: Pal, Parameswar;Schafer, Marcus C.;Hendrich, Michael P.;Ryabov, Alexander D.;Collins, Terrence J.
• 通讯作者: Collins, Terrence J.

Artificial Metalloproteins with Dinuclear Iron-Hydroxido Centers.

• DOI: 10.1021/jacs.0c12564
• 发表时间: 2021-02-10
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Miller KR;Biswas S;Jasniewski A;Follmer AH;Biswas A;Albert T;Sabuncu S;Bominaar EL;Hendrich MP;Moënne-Loccoz P;Borovik AS
• 通讯作者: Borovik AS