Mechanism of Mitochondrial Fe-S Cluster Assembly

线粒体Fe-S簇组装机制

• 批准号: 0111161
• 负责人: James Cowan
• 金额: --
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0111161&HistoricalAwards=false
• 关键词: Mechanism; Mitochondrial; Fe; Cluster; Assembly

Dr. James A. Cowan, Chemistry Department, Ohio State University, is supported by the Inorganic, Bioinorganic, and Organometallic Chemistry Program of the Chemistry Division for investigations into the mechanism of mitochondrial Fe-S cluster assembly. Recent characterization of gene products that are putatively involved in biosynthetic cluster assembly allows consideration of a range of molecular mechanisms that underlie the chemistry of cluster biogenesis. The understanding of the details of the cellular pathways requires the characterization of such proteins and the elucidation of their functional chemistry. Accordingly, this project will focus on a systematic investigation of two proteins implicated in mitochondrial ironsulfur cluster biosynthesis: IscU and IscA. The structure and function of these Fe-S cluster-containing proteins will be characterized. Particular attention will be paid to the elucidation of cognate protein partners, mechanisms of iron/sulfur transfer, and the role of redox chemistry in mediating these pathways.Iron sulfur clusters are essential metal cofactors that are involved in mitochondrial respiration, cell signaling pathways, transcriptional and translational control in gene regulation, metal ion homeostasis, the biological chemistry of reactive oxygen species, and novel mechanisms for enzymatic catalysis. This study will probe the fundamental, but as yet unanswered questions of how such centers are synthesized in vivo, what proteins are involved in the syntheses, and how the proteins function?

James A. Cowan博士，俄亥俄州立大学化学系，受化学学部无机、生物无机和有机金属化学项目的支持，研究线粒体Fe-S簇组装的机制。最近的基因产物表征，被认为是参与生物合成簇组装允许考虑一系列分子机制的基础上的化学簇生物发生。要了解细胞通路的细节，就需要对这些蛋白质进行表征，并阐明它们的功能化学。因此，本项目将集中于系统研究涉及线粒体铁硫簇生物合成的两种蛋白质：IscU和IscA。这些含Fe-S簇的蛋白质的结构和功能将被表征。将特别关注同源蛋白伴侣的阐明，铁/硫转移的机制，以及氧化还原化学在介导这些途径中的作用。铁硫簇是必需的金属辅助因子，参与线粒体呼吸、细胞信号通路、基因调控中的转录和翻译控制、金属离子稳态、活性氧的生物化学以及酶催化的新机制。这项研究将探索这些中心是如何在体内合成的，哪些蛋白质参与了合成，以及这些蛋白质如何起作用的基本问题，但尚未得到解答。