XAS CHARACTERIZATION OF THE IRON ACTIVE SITES IN PROTEINS INVOLVED IN IRON HOMEO

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 弗里德赖希共济失调是一种常染色体心脏和神经退行性疾病，影响1/50，000的人，是由于无法产生足够量的蛋白共济失调蛋白引起的。Frataxin对于铁稳态的细胞控制是必不可少的，并且被认为充当将线粒体Fe（II）递送至酶亚铁螯合酶和ISU装置以分别完成血红素和[2Fe-2S]簇生物组装的铁伴侣。此外，据信共济失调蛋白通过调节蛋白质结合铁的氧化态来控制活性氧物质的产生。我们实验室的长期目标是在原子水平上表征蛋白质如何控制血红素和Fe-S簇生物合成过程中的铁传递和金属反应性。在本提案中，我们将扩展我们之前的XAS提案，旨在了解frataxin如何结合铁，以了解铁辅因子生产过程中金属是如何传递和利用的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.