EXAFS STUDIES OF NONHEME IRON ENZYMES AND MODEL COMPOUNDS

非血红素铁酶和模型化合物的 EXAFS 研究

• 批准号: 8170045
• 负责人: LAWRENCE QUE, JR
• 金额: $ 1.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170045
• 关键词: Address; Cephalosporins; Computer Retrieval of Information on Scientific Projects Database; Dioxygen; Electrons; Enzymes; Funding; Grant; Institution; Iron; Modeling; Penicillins; Play; Research; Research Personnel; Resources; Roentgen Rays; Role; Source; Spectrum Analysis; Structure; Time; United States National Institutes of Health; absorption; alpha ketoglutarate; enzyme model; ferryl iron; insight; interest; oxidation; perferryl iron

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. Nonheme iron enzymes catalyze a broad range of metabolically important transformations by activating dioxygen. In the proposed mechanisms of those enzymes, dioxygen is reduced one electron at a time to afford in turn iron(III)-superoxo, iron(III)-peroxo or hydroperoxo, and iron(IV)-oxo intermediates. An important strategy to gain insight into these mechanisms is by trapping and characterizing such intermediates either during enzyme turnover or in functional models of such enzymes. X-ray absorption spectroscopy has played a key role in establishing the structures of these trapped intermediates. In the following SSRL two-year period, we will study MMO intermediates P and Q in the presence of CD4, as well as high-valent iron-oxo intermediates of interest, including the first iron(V)-oxo species and new diiron(III,IV) and diiron(IV) intermediates, some of which will be generated by electrochemical oxidation. Studies on DAOCS, the 2-oxoglutarate-dependent enzyme that converts penicillin to cephalosporin, will also be initiated to address a mechanistic question posed by an unexpected crystallographic result.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 非血红素铁酶通过激活二恶英催化了广泛的代谢重要转化。在这些酶的提出的机制中，二氧化物一次降低一个电子，以负担得起铁（iii） - 苏福氧，铁（III） - 过氧或氢过氧和铁（IV） - 氧中间体。洞悉这些机制的一个重要策略是在酶离职期间或此类酶的功能模型中捕获和表征此类中间体。 X射线吸收光谱在建立这些被困中间体的结构中起着关键作用。在接下来的SSRL两年期间，我们将在存在CD4的情况下研究MMO中间体P和Q，以及感兴趣的高价值铁氧中间体，包括第一种铁（V） - 氧化物种和新的Diiron（III，IV）和Diiron（IV）和Diiron（IV）和二烷（IV）中间体，其中一些是由氧气产生的，这些氧气会产生由电动机产生的。对DAOC的研究，将青霉素转化为头孢菌素的2-氧基谷物依赖性酶也将开始解决因意外晶体学结果而提出的机械问题。