Nitrogenase assembly mechanism

固氮酶组装机制

• 批准号: 9309973
• 负责人: Markus W Ribbe
• 金额: $ 30.99万
• 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/9309973
• 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 固氮酶反应代表了支持植物生长的氮的可用形式的主要来源。 人口的存在。因此，了解构建块有多小 组装成功能性固氮酶实体与人类健康显著相关。使用 结合遗传、生物化学、光谱和结构方法，我们建议 研究钼固氮酶M-和P-簇如何通过独特的 将生化反应转化为功能单位。具体来说，我们将研究两个4Fe 通过自由基SAM依赖的方式， 碳化物插入伴随着“第九”硫的掺入，两个4Fe模块是如何 重排和耦合成8 Fe的P-集群通过独特的氧化还原反应伴随着 去除“第八”硫，以及各种组装蛋白如何相互作用， 促进M-和P-簇的成熟。通过我们建议的研究，我们希望 进一步完善固氮酶独特金属簇的生物合成途径，这将 为这种重要酶的结构-功能关系提供了重要的见解， 揭示了复杂集群装配机理的一些一般性原理， 生物系统。