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）：固氮酶是一种复杂的金属酶，可催化生物系统中最显着的化学转化之一：将大气中的二氮依赖于核苷酸还原为生物可利用的氨。人们对解码固氮酶的组装机制有着浓厚的兴趣，不仅因为它与固氮酶特异性反应的显着相关性，而且因为它对一般金属蛋白生物发生的巨大影响。在这里，我们建议通过结合遗传、生化、光谱和结构方法来极大地扩展我们对固氮酶组装过程的理解。维氏固氮菌钼固氮酶的 MoFe 蛋白将是本次研究的重点。通过我们提出的研究，我们期望进一步完善MoFe蛋白及其相关簇的生物合成途径，不断努力，最终目标是揭示固氮酶组装的分子机制。此外，使用固氮酶作为模型系统，我们还希望提供生物金属簇组装的一般主题，从长远来看，这可能有助于开发复杂金属簇化学合成的成功策略。 。公共卫生相关性：固氮酶催化大气中的氮转化为生物可利用的氨，从而提供还原氮，这是人类生存所需的核酸和蛋白质的重要​​组成部分。这项特别的提案涉及固氮酶 MoFe 蛋白及其相关金属簇的组装，这些研究的结果有望提供生物金属簇组装的一般主题，并促进未来开发具有成本效益的催化活性金属簇化学合成策略。因此，我们提出的研究除了与人类健康的内在相关性之外，还可能具有额外的经济价值。