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

铁 HOMEO 涉及的蛋白质中铁活性位点的 XAS 表征

• 批准号: 7722028
• 负责人: TIMOTHY Louis STEMMLER
• 金额: $ 0.23万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722028
• 关键词: Active Sites; Affect; Anabolism; Binding; Computer Retrieval of Information on Scientific Projects Database; Enzymes; Friedreich Ataxia; Funding; Goals; Grant; Heme; Homeostasis; Human; Institution; Iron; Iron-Binding Proteins; Laboratories; Metals; Mitochondria; Molecular Chaperones; Neurodegenerative Disorders; Production; Proteins; Reactive Oxygen Species; Research; Research Personnel; Resources; Source; United States National Institutes of Health; cofactor; ferrochelatase; frataxin; oxidation

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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，影响五万分之一的人类，是由于无法产生足够量的弗拉塔辛蛋白引起的。 Frataxin 对于铁稳态的细胞控制至关重要，并且被认为可作为铁伴侣，将线粒体 Fe(II) 递送至亚铁螯合酶和 ISU 装置，分别完成血红素和 [2Fe-2S] 簇的生物组装。此外，frataxin被认为可以通过调节蛋白质结合铁的氧化态来控制活性氧的产生。我们实验室的长期目标是在原子水平上表征蛋白质如何在血红素和 Fe-S 簇生物合成过程中控制铁的输送和金属反应性。在本提案中，我们将扩展之前的 XAS 提案，旨在了解 frataxin 如何结合铁，以了解金属在 Fe 辅因子生产过程中如何输送和利用。