This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Friedreich's ataxia, an autosomal cardio- and neurodegenerative disorder affecting 1 in 50,000 humans, is caused by the inability to produce sufficient amounts of the protein frataxin. Frataxin is essential for the cellular control of iron homeostasis and is believed to serve as an iron chaperone that delivers mitochondrial Fe(II) to the enzymes ferrochelatase and the ISU apparatus for completion of heme and [2Fe-2S] cluster bioassembly, respectively. In addition, frataxin is believed to control reactive oxygen species production by modulating the oxidation state of protein bound iron. A longrange goal of our laboratory is to characterize, at the atomic level, how proteins control iron delivery and metal reactivity during heme and Fe-S cluster biosynthesis. In this proposal, we will expand on our previous XAS proposal, directed at understanding how frataxin binds iron, to provide an understanding of how metal is delivered and utilized during Fe cofactor production.
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