STRUCTURE AND MECHANISM OF AROMATIC OXIDIZING ENZYMES

芳香族氧化酶的结构与机理

• 批准号: 8361675
• 负责人: Matthew H Sazinsky
• 金额: $ 0.37万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361675
• 关键词: Active Sites; Aromatic Compounds; Bacteria; Chemicals; Chemistry; Cresol; Cresols; Electrons; Enzymes; Epoxy Compounds; FADH2; FMN reductase; Flavoproteins; Food Energy; Funding; Grant; Hydrocarbons; Mixed Function Oxygenases; Mono-S; NADH; National Center for Research Resources; Oxygenases; Pathway interactions; Principal Investigator; Research; Research Infrastructure; Resources; Source; Structure; System; Time; Toluene; United States National Institutes of Health; analog; cost; oxidation; structural biology; toluene 2-xylene monooxygenase

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. The toluene /o-xylene monooxygenase (ToMO) system catalyzes the NADH dependant mono-oxidation of aromatic compounds like toluene to cresol at a diiron active site. This first catalytic step is essential for the utilization of these hydrocarbons as sources of food and energy for certain bacteria. Extensive studies have been carried to understand how diiron centers carry out their chemistry and assemble all the necessary substrates (electrons, O2, and hydrocarbon) at the active site in the hydroxylase component and control the timing of their reactivity so as to avoid quenching of intermediates. The most recent round of structural studies aimed to identify the pathway in the 250 kDa hydroxylase by which O2 gains access to the diiron center enzyme. Like, ToMO, styrene monooygenase, is essential for initializing the breakdown of aromatics like styrene into useful metabolites. Styrene monooxygenase is a two component flavoprotein. In this system, an NADH- flavin oxidoreductase, SMOB, delivers FADH2 to the oxygenase component, SMOA, where it converts styrene and chemical analogues to epoxides. Recently the structure of SMOA was determined. The current focus is to determine the structure of SMOB and understand how it transfers FADH2 to SMOB.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 甲苯/邻二甲苯单加氧酶 (ToMO) 系统在二铁活性位点催化芳香族化合物（如甲苯）依赖 NADH 的单氧化反应生成甲酚。 第一个催化步骤对于利用这些碳氢化合物作为某些细菌的食物和能源来源至关重要。 为了了解二铁中心如何进行化学反应并在羟化酶组分的活性位点组装所有必需的底物（电子、O2 和碳氢化合物）并控制其反应时间以避免中间体猝灭，已经进行了广泛的研究。 最近一轮的结构研究旨在确定 250 kDa 羟化酶中 O2 获取二铁中心酶的途径。 例如，ToMO（苯乙烯单加酶）对于将苯乙烯等芳香族化合物初步分解为有用的代谢物至关重要。 苯乙烯单加氧酶是一种双组分黄素蛋白。 在该系统中，NADH-黄素氧化还原酶 SMOB 将 FADH2 传递至加氧酶成分 SMOA，在此将苯乙烯和化学类似物转化为环氧化物。 最近SMOA的结构被确定。 当前的重点是确定 SMOB 的结构并了解它如何将 FADH2 转移到 SMOB。