XAS OF THE INTERMEDIATE FORMED DURING THE REACTIONS OF P450S AND PEROXYNITRITE

P450S 与过氧亚硝酸盐反应过程中形成的中间体的 XAS

• 批准号: 8362266
• 负责人: MICHAEL T. GREEN
• 金额: $ 0.14万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362266
• 关键词: Acids; Alzheimer' s Disease; Cardiovascular Diseases; Cytochrome P450; Disease; Funding; Grant; Hemeproteins; Hydroxide Ion; Hydroxides; National Center for Research Resources; Neurodegenerative Disorders; Nitrates; Oxidants; Parkinson Disease; Peracetic Acid; Peroxonitrite; Play; Principal Investigator; Proteins; Radiation; Reaction; Reporting; Research; Research Infrastructure; Resources; Role; Source; Tyrosine; United States National Institutes of Health; cost; nitration; structural biology

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. Typically peroxynitrite (PN) inactivates thiolate-ligated hemes proteins through tyrosine nitration. These nitrated proteins are detected and thought to play a role in diseases such as Parkinson?s and Alzheimer?s. They also have been shown to have a significant presence in neurodegenerative and cardiovascular disorders. Ullrich and coworkers reported that the reaction of PN with P450?s yielded P450 compound II (an Fe(IV)hydroxide species, similar to the rebound intermediate of cytochrome P450). The ?P450-II? thus formed was unusual in that it was relatively stable and could be produced in high yield. The yield and stability of the P450-PN intermediate are in stark contrast to the results obtained when P450-II is generated with more traditional oxidants (e.g. peracetic acid or meta-chloroperbenzoic acid).

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 通常，过氧亚硝酸盐（PN）通过酪氨酸硝酸化会使硫醇酸盐绑扎的Hemes蛋白失活。这些硝化蛋白被发现并被认为在帕金森氏症和阿尔茨海默氏症等疾病中起作用。 它们还被证明在神经退行性和心血管疾病中具有重要的存在。 Ullrich及其同事报告说，PN与P450的反应产生了P450化合物II（Fe（IV）氢氧化物物种，类似于细胞色素P450的反弹中间体）。 p450-ii？因此形成的是不寻常的，因为它相对稳定，并且可以高产量产生。 P450-PN中间体的产率和稳定性与使用更传统的氧化剂（例如过乙酸或元氯苯甲酸）产生P450-II获得的结果形成鲜明对比。