Mechanism of Mitochondrial Fe-S Cluster Assembly

James A.科万，化学系，俄亥俄州州立大学，是由无机，生物无机和有机化学计划的化学部的研究线粒体Fe-S簇组装的机制。最近的表征基因产物，pueretically参与生物合成集群组装允许考虑一系列的分子机制，集群生物发生的化学基础。细胞通路的细节的理解需要这些蛋白质的表征和阐明其功能化学。因此，本项目将集中在线粒体铁硫簇生物合成中涉及的两个蛋白质：IscU和IscA的系统研究。这些铁硫簇蛋白的结构和功能的特点。铁硫簇是重要的金属辅因子，参与线粒体呼吸、细胞信号转导、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、细胞内的铁硫代谢、铁硫代谢等过程。和酶催化的新机制。这项研究将探讨基本的，但尚未回答的问题，这些中心是如何在体内合成的，什么蛋白质参与合成，以及蛋白质如何发挥作用？

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?