Nitrogenase assembly mechanism

固氮酶组装机制

• 批准号: 9700327
• 负责人: Markus W Ribbe
• 金额: $ 10万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9700327
• 关键词: Biochemical; Biochemical Reaction; Biomimetics; Chemicals; Chimeric Proteins; Complex; Coupled; Enzymes; Event; Excision; Genetic; Health; Human; Investigation; Knowledge; Molybdenum; Nitrogen; Nitrogenase; Oxidation-Reduction; Pathway interactions; Population; Proteins; Reaction; Research; Role; Source; Sulfur; Variant; biological systems; catalyst; chemical synthesis; insight; interstitial; oxidation

PROJECT SUMMARY Nitrogenase reaction represents a major source of the usable form of nitrogen that supports the existence of human population. As such, understanding how small building blocks are assembled into a functional nitrogenase entity is of significant relevance to human health. Using combined genetic, biochemical, spectroscopic and structural approaches, we propose to investigate how M- and P-clusters of molybdenum nitrogenase are assembled via unique biochemical reactions into functional units. Specifically, we will investigate how two 4Fe modules are rearranged and coupled into an 8Fe core of M-cluster via radical SAM-dependent carbide insertion concomitant with the incorporation of a “9th” sulfur, how two 4Fe modules are rearranged and coupled into an 8Fe P-cluster via unique redox reactions concomitant with the removal of an “8th” sulfur, and how various assembly proteins interact with one another to facilitate the maturation of M- and P-clusters. Through our proposed studies, we expect to further refine the biosynthetic pathways of the unique metalloclusters of nitrogenase, which will provide crucial insights into the structural-functional relationship of this important enzyme and reveal some general principles of the assembly mechanisms of complex metalloclusters in biological systems.

项目摘要 氮酶反应代表了支持氮的可用形式的主要来源 人口的存在。因此，了解构建块的小 组装成功能性氮酶实体与人类健康具有重要意义。使用 遗传，生化，光谱和结构方法结合，我们建议 研究如何通过独特组装钼酶的m-和p簇 生化反应成功能单位。具体来说，我们将研究两个4fe 模块被重新排列，并通过激进的SAM依赖性耦合到M-Cluster的8FE核心 与掺入“ 9”硫的碳化物插入，两个4FE模块是如何 通过与唯一的氧化还原反应与与 去除“第八”硫，各种组装蛋白如何相互作用 促进M-和P群集的成熟。通过我们提出的研究，我们希望 进一步完善氮酶独特金属群的生物合成途径，该途径将 提供有关这种重要酶和的结构功能关系的关键见解 揭示复杂金属散光器组装机制的一些一般原理 生物系统。