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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Friedreich‘s共济失调是一种常染色体心脏和神经退行性疾病，每50,000人中就有1人受到影响，原因是无法产生足够数量的蛋白质Frataxin。Frataxin对细胞内铁稳态的控制是必不可少的，被认为是一种铁伴侣，将线粒体Fe(II)分别输送到铁络合酶和ISU装置，以完成血红素和[2Fe-2S]簇的生物组装。此外，Frataxin被认为通过调节蛋白质结合铁的氧化状态来控制活性氧的产生。我们实验室的一个长期目标是在原子水平上表征蛋白质如何在血红素和铁-S簇状生物合成过程中控制铁的输送和金属的反应。在这份提案中，我们将扩展我们之前的XAS提案，旨在了解Frataxin如何与铁结合，以提供对在铁辅料生产过程中金属是如何输送和利用的理解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.