Biological Activation of Small Molecules: Nitrogenases and Related Biomimetic Models

小分子的生物活化：固氮酶和相关仿生模型

• 批准号: 0744820
• 负责人: Robert Szilagyi
• 金额: $ 45万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0744820&HistoricalAwards=false
• 关键词: Biological; Activation; Small; Molecules; Nitrogenases

Biological nitrogen fixation provides about half of the metabolically accessible nitrogen in nature, which is a fundamental basis of life on earth. This is carried out at ambient conditions from abundant atmospheric dinitrogen by a fascinating metalloenzymatic machinery. This project aims to address some of the fundamental questions about the structure and molecular mechanism of this machinery that remain unanswered despite decades of past research. The approach has the potential to contribute significantly to the design of functionally analogous biomimetic systems for agricultural and chemical technological use. A set of physical-chemical parameters will be established that is required for the activation and reduction of the N-N triple bond in dinitrogen at iron-sulfur cluster-based compounds. The chemical composition of the unknown interstititial ligand at the active site cofactor center of the Mo-containing nitrogenase metalloenzyme will be determined. Building on the above two tasks, an in silico, virtual chemical model of the metalloenzyme active site will be created, which is a long needed tool for probing the intimate molecular details of substrate binding, proton, and electron-transfer, substrate activation and transformation, and product release processes. These will be achieved by employing an innovative combination of the multi-edge X-ray absorption spectroscopic technique and a range of computational methods. Due to the complex nature of the above tasks, the research will be carried out in a multidisciplinary environment involving biochemists and enzymologists, spectroscopists, inorganic and computational chemists that will provide a unique environment for scientific discovery and student training at undergraduate, graduate, and postdoctoral levels. Broader Impact: The main scientific achievement of the project will be the specific understanding of how ligand/protein environment and cluster composition can influence the structure and reactivity of heterometal substituted iron-sulfur clusters with relevance to nitrogen fixation. This knowledge will be incorporated into a computational model of the nitrogenase active site that looks and acts in silico like the real metalloenzyme in vitro. The methodology developed is likely to impact research efforts toward the catalytic mechanism of other iron-sulfur containing metalloenzymes. As part of student training, the principal investigator's students will learn the fine details of metalloenzymatic and biomimetic sample preparations from collaborators. Conversely, the principal investigator will train the collaborators' students in synchrotron science, physical inorganic chemistry, and computational chemistry. The research activities and scientific insights will be disseminated via peer-reviewed journals, conferences and meetings, and electronically via the research group's website.

生物固氮提供了自然界中约一半的代谢可利用氮，这是地球生命的基本基础。这是在环境条件下进行的丰富的大气中的双氮由一个迷人的金属酶机制。该项目旨在解决一些关于这种机制的结构和分子机制的基本问题，尽管过去几十年的研究仍然没有答案。该方法有可能大大有助于农业和化学技术使用的功能类似的仿生系统的设计。将建立一组物理化学参数，这是所需的活化和还原的N-N三键的二氮在铁-硫簇基化合物。将测定含钼固氮酶金属酶活性位点辅因子中心的未知半胱氨酸配体的化学组成。基于上述两项任务，将创建金属酶活性位点的计算机虚拟化学模型，这是一个长期需要的工具，用于探测底物结合，质子和电子转移，底物活化和转化以及产物释放过程的分子细节。这些将通过采用多边缘X射线吸收光谱技术和一系列计算方法的创新组合来实现。由于上述任务的复杂性，研究将在涉及生物化学家和酶学家，光谱学家，无机和计算化学家的多学科环境中进行，这将为本科，研究生和博士后水平的科学发现和学生培训提供独特的环境。更广泛的影响：该项目的主要科学成果将是对配体/蛋白质环境和簇组成如何影响与固氮相关的杂金属取代的铁硫簇的结构和反应性的具体理解。这些知识将被纳入固氮酶活性位点的计算模型中，该模型在计算机上看起来和在体外的真实的金属酶一样。开发的方法可能会影响其他含铁硫金属酶催化机制的研究工作。作为学生培训的一部分，主要研究者的学生将从合作者那里学习金属酶和仿生样品制备的细节。 相反，首席研究员将在同步加速器科学，物理无机化学和计算化学方面培训合作者的学生。研究活动和科学见解将通过同行评审期刊、大会和会议以及研究小组网站的电子版传播。