SUBSTRATE COORDINATION IN RADICAL SAM DEHYDROGENASES

自由基 SAM 脱氢酶中的底物配位

• 批准号: 8362330
• 负责人: ROBERT A SCOTT
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362330
• 关键词: Alcohols; Binding; Catalysis; Electron Transport; Electrons; Enzymes; Funding; Grant; Hydrogen; Modeling; National Center for Research Resources; Oxidoreductase; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Source; Sulfhydryl Compounds; Testing; United States National Institutes of Health; Work; abstracting; analog; cost; oxidation; structural biology

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. 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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 自由基SAM脱氢酶利用5‘-脱氧腺苷自由基(5’-da？)通过含有未成对电子的中间体对醇或硫醇进行双电子氧化。那个5英尺长的？通过提取底物上的关键氢原子来启动催化。最近，ATSB是一种自由基SAM酶，催化同源蛋白质上的丝氨酸残基氧化成甲酰甘氨基(FGly)残基，其表征表明它含有三个[4Fe？4S]簇，并提出了一个工作模型，认为其中一个簇与底物接触，通过内球电子转移促进底物自由基中间体的第二电子损失。这项研究的目的是通过模拟底物来验证这一模型，在底物中相关的丝氨基残基被硒半胱氨酸残基取代，并用Se-XAS分析相互作用。