Mechanisms of Binuclear Non-Heme Iron Enzymes

双核非血红素铁酶的机制

• 批准号: 6740052
• 负责人: MICHAEL D CLAY
• 金额: $ 4.3万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740052
• 关键词: Raman spectrometry; active sites; chemical structure; computational biology; electron spin resonance spectroscopy; enzyme mechanism; enzyme structure; ferritin; infrared spectrometry; iron; postdoctoral investigator; structural biology

DESCRIPTION (provided by applicant): Binuclear non-heme iron active sites are present in a wide variety of proteins and enzymes which perform different biological functions. This proposal will specifically investigate those sites present in sMMO, R2, D9D and frog M-ferritin to elucidate their differences in dioxygen reactivity (i.e. hydroxylation, radical generation, desaturation and ferroxidation). These differences have led to the identification of various diiron peroxy (P) and high-valent (Q and X) intermediates. While these enzymatic intermediates have been investigated, relatively little is known about their geometric and electronic structure and, more importantly, how their structure relates to reactivity. Therefore, the major objectives of this research proposal are to use biophysical spectroscopic techniques (EPR, resonance Raman and UV-vis/Near IR absorption/CDNTVH MCD) to characterize the geometric, electronic and magnetic properties of the various diiron peroxy (P) and high-valent (Q and X) intermediates in these enzymes and relevant model complexes and apply computational methodologies to gain greater insight into the mechanistic conversion between these intermediates.

描述（由申请人提供）：双核非血清铁活性位点存在于多种蛋白质和酶中，这些蛋白质和酶执行不同的生物学功能。该建议将特别研究SMMO，R2，D9D和Frog M-Frog M-Freritin中的那些位点，以阐明它们在二氧化反应性方面的差异（即羟基化，自由基产生，脱饱和和铁氧化）。这些差异导致鉴定了各种二铁（P）和高价值（Q和X）中间体。尽管已经研究了这些酶促中间体，但对它们的几何结构和电子结构的了解相对较少，更重要的是，它们的结构如何与反应性相关。因此，这项研究建议的主要目标是使用生物物理光谱技术（EPR，EPR，共振拉曼和UV-VIS/近IIR吸收/CDNTVH MCD）来表征各种二铁（P）和高元素的各种二型铁（Q and Q）和高度（q和x）的几何和磁性的几何，电子和磁性，以及这些启用（q和x）的相关性（q和x）互联母以及相关的启用性（q和x）的互联母，以及在这些启用（q和x）中的相关性，以及这些启用的启用量和X型中的互动性。深入了解这些中间体之间的机械转换。