SUBSTRATE COORDINATION IN RADICAL SAM DEHYDROGENASES

自由基 SAM 脱氢酶中的底物配位

• 批准号: 8170334
• 负责人: ROBERT A SCOTT
• 金额: $ 0.03万
• 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/8170334
• 关键词: Alcohols; Binding; Catalysis; Computer Retrieval of Information on Scientific Projects Database; Electron Transport; Electrons; Enzymes; Funding; Grant; Hydrogen; Institution; Modeling; Oxidoreductase; Proteins; Research; Research Personnel; Resources; Source; Sulfhydryl Compounds; Testing; United States National Institutes of Health; Work; abstracting; analog; oxidation

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. Radical SAM dehydrogenases use the oxidizing power of a 5'-deoxyadenosyl radical (5'-dA?) to carry out two-electron oxidations of alcohols or thiols via intermediates containing unpaired electrons. The 5'-dA? initiates catalysis by abstracting a key hydrogen atom on the substrate. Recently, characterization of AtsB, a radical SAM enzyme that catalyzes the oxidation of a seryl residue on a cognate protein to a formylglycyl (fGly) residue, showed that it contained three [4Fe?4S] clusters, and a working model was put forth that suggested that one of the clusters binds in contact with the substrate to facilitate loss of the second electron from a substrate radical intermediate by inner-sphere electron transfer. This study aims to test this model by using an analog of the substrate in which the relevant seryl residue is replaced by a selenocysteinyl residue and analyzing for the interaction by Se XAS.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 自由基 SAM 脱氢酶利用 5'-脱氧腺苷自由基 (5'-dA?) 的氧化能力，通过含有不成对电子的中间体对醇或硫醇进行双电子氧化。 5'-dA？通过提取底物上的关键氢原子来启动催化。最近，AtsB（一种自由基 SAM 酶，催化同源蛋白上的丝氨酰残基氧化为甲酰甘氨酰 (fGly) 残基）的表征表明，它含有三个 [4Fe?4S] 簇，并提出了一个工作模型，表明其中一个簇与底物接触结合，以促进底物自由基中间体失去第二个电子。 通过内层电子转移。本研究旨在通过使用底物类似物（其中相关丝氨酰残基被硒代半胱氨酰残基取代）并通过 Se XAS 分析相互作用来测试该模型。