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).

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。 典型地，过氧亚硝酸盐（PN）通过酪氨酸硝化使硫醇盐连接的血红素蛋白失活。这些被硝化的蛋白质被检测到，并被认为在帕金森等疾病中发挥作用。老年痴呆症？S. 它们还被证明在神经退行性疾病和心血管疾病中具有显著的存在。 Ullrich和同事报道，PN与P450的反应？S得到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）。 什么？P450-II？如此形成的不寻常之处在于它相对稳定并且可以高产率生产。 P450-PN中间体的产率和稳定性与使用更传统的氧化剂（例如过乙酸或间氯过苯甲酸）生成P450-II时获得的结果形成鲜明对比。