Nitrogenase Assembly Mechanism

固氮酶组装机制

• 批准号: 7990403
• 负责人: Markus W Ribbe
• 金额: $ 29.02万
• 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 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990403
• 关键词: Address; Ammonia; Azotobacter vinelandii; Binding Sites; Bioavailable; Biochemical; Biogenesis; Biological; Biological Models; Chemicals; Complex; Development; Funding; Future; Genetic; Goals; Health; Human; In Situ; Investigation; Metalloproteins; Metals; Molecular; Molybdenum; Molybdoferredoxin; Nitrogen; Nitrogenase; Nucleic Acids; Nucleotides; Outcome Study; Pathway interactions; Population; Process; Proteins; Reaction; Research; Role; Site; biological systems; chemical synthesis; cost; economic value; interest; metalloenzyme

DESCRIPTION (provided by applicant): Nitrogenase is a complex metalloenzyme that catalyzes one of the most remarkable chemical transformations in biological systems: the nucleotide-dependent reduction of atmospheric dinitrogen to bioavailable ammonia. There is an outstanding interest in decoding the assembly mechanism of nitrogenase, not only because of its significant relevance to nitrogenase-specific reactions, but also because of its tremendous implication for general metalloprotein biogenesis. Here we propose to greatly expand our understanding of the nitrogenase assembly process by combined genetic, biochemical, spectroscopic and structural approaches. The MoFe protein of the molybdenum nitrogenase of Azotobacter vinelandii will be the focus of the proposed investigation. Through our proposed studies, we expect to further refine the biosynthetic pathways of MoFe protein and its associated clusters, a continuous effort with an ultimate goal to unravel the molecular mechanism of nitrogenase assembly. Furthermore, using nitrogenase as a model system, we also hope to provide general themes of biological metal cluster assembly, which may, in the long run, prove instrumental in developing successful strategies for the chemical synthesis of complex metalloclusters. . PUBLIC HEALTH RELEVANCE: Nitrogenase catalyzes the transformation of atmospheric dinitrogen to bioavailable ammonia, thereby supplying the reduced nitrogen, an essential component of nucleic acids and proteins, for the existence of human population. This particular proposal deals with the assembly of nitrogenase MoFe protein and its associated metalloclusters and the outcome of these studies will hopefully provide general themes of biological metal cluster assembly and facilitate future development of cost-efficient strategies for the chemical synthesis of catalytically active metalloclusters. As such, our proposed research may have additional economic value in addition to its intrinsic relevancy to human health.

描述（由申请人提供）：氮酶是一种复杂的金属酶，它催化生物系统中最显着的化学转化之一：核苷酸依赖性减少大气二致变化为生物可利用的氨。在解码氮酶的装配机理方面非常感兴趣，这不仅是因为它与氮酶特异性反应的重要性，而且还因为它对一般金属蛋白生物发生的巨大意义。在这里，我们建议通过结合遗传，生化，光谱和结构方法来大大扩展对氮酶组装过程的理解。替氏拟杆菌的钼氮的MOFE蛋白将是拟议研究的重点。通过我们提出的研究，我们希望进一步完善MOFE蛋白质及其相关簇的生物合成途径，这是一个持续的努力，以最终的目标揭示了氮酶组装的分子机制。此外，我们还希望使用氮气作为模型系统，希望提供生物金属簇组装的一般主题，从长远来看，这可能会证明有助于开发成功合成复杂金属簇的化学策略。 。公共卫生相关性：氮酶催化了大气二氮对生物利用氨的转化，从而为人口的存在提供了减少的氮，核酸和蛋白质的重要​​组成部分。该特定的建议涉及氮酶MOFE蛋白及其相关的金属群体的组装，并且这些研究的结果将有望提供生物金属簇组装的一般主题，并促进未来的成本效率策略，用于催化活性金属激素的化学化学综合。因此，除了与人类健康的内在相关性外，我们提出的研究还可能具有额外的经济价值。