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: 7722030
• 负责人: LAWRENCE QUE, JR
• 金额: $ 0.4万
• 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/7722030
• 关键词: Address; Cephalosporins; Computer Retrieval of Information on Scientific Projects Database; Dioxygen; Electrons; Enzymes; Funding; Grant; Institution; Iron; Modeling; Penicillins; Play; Range; 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.

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。 非血红素铁酶通过激活氧气来催化一系列代谢上重要的转化。在提出的这些酶的机制中，氧一次还原一个电子，依次生成铁(III)-超氧，铁(III)-过氧基或氢过氧基，以及铁(IV)-氧代中间体。深入了解这些机制的一个重要策略是在酶的周转过程中或在这些酶的功能模型中捕获和表征这些中间体。X射线吸收光谱在确定这些被捕获的中间体的结构方面发挥了关键作用。在接下来的两年SSRL期间，我们将研究在CD4存在下的MMO中间体P和Q，以及感兴趣的高价铁氧中间体，包括第一个铁(V)-氧物种和新的双铁(III，IV)和双铁(IV)中间体，其中一些中间体将通过电化学氧化产生。对DAOCS的研究也将启动，以解决一个意外的结晶学结果提出的机制问题。DAOCS是一种依赖于2-氧戊二酸的酶，用于将青霉素转化为头孢菌素。