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?
