S K-EDGE XAS STUDIES AS A PROBE OF ELECTRONIC STRUCTURE/CONTRIBUTION TO FUNCTION

SK-EDGE XAS 研究作为电子结构/功能贡献的探针

• 批准号: 8362398
• 负责人: BRITT HEDMAN
• 金额: $ 0.03万
• 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/8362398
• 关键词: Active Sites; Biochemical Reaction; Complex; DNA glycosylase; Electrons; Enzymes; Escherichia coli; Family; Ferredoxin; Funding; Grant; Hydrogen Bonding; Iron; Ligands; Lyase; Metals; Methodology; Modeling; Mono-S; Mutation; National Center for Research Resources; Principal Investigator; Protein Binding; Pyruvate; Radiation; Research; Research Infrastructure; Resources; Series; Site; Solvents; Source; Spectrum Analysis; Structure; Sulfur; System; United States National Institutes of Health; cost; desaturase; dimethyl sulfoxide reductase; electronic structure; enzyme model; protein complex; structural biology; sulfite oxidase

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. Ligand K-edge XAS provides a direct probe of ligand metal bonding. We have developed this methodology to investigate the electronic structures of model complexes and protein active-sites of a number of clusters and sites, in particular Fe-S, Cu-S clusters and dithiolene-containing Mo/W sites. In the previous proposal period, among several studies, we evaluated the generality of the difference between HiPIPs and ferredoxins and systematically studied the effect of H-bonding, solvent interaction and effect of changing dielectric field around these and other clusters using well-characterized model complexes and proteins, and combined experimental results with DFT calculation. We have also developed the bonding/geometric structure correlations in the Mo(tris)dithiolenes and the mechanism of oxo trasnsfer in the DMSO reductase family of enzymes and models. In this proposal we plan to extend this methodology, and combine it with complementary spectroscopies, to study several Fe-S systems, such as the interaction of SAM with the Fe4S4 cluster in pyruvate lyase activating enzyme; MutY - a DNA glycosylase from Escherichia coli; Fe2S2 protein binding to ?9 desaturase; and effects of Cys->Ser mutations on electron delocalization in iron sulfur clusters. We also intend to study a series of Mo mono- and bis-oxo bis(dithiolene) complexes that model the states of the sulfite oxidase family. The specific aim is to define the electronic structure of enzymes and model complexes and understand the correlations between structure and function of enzymatic reactions.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 配体K-边缘XAS提供了配体金属键合的直接探针。我们已经开发了这种方法来研究许多簇和位点的模型复合物和蛋白质活性位点的电子结构，尤其是Fe-S，Cu-S簇和含二硫烯的MO/W位点。在上一项提案期间，在几项研究中，我们评估了HIPIPS和铁蛋白之间差异的一般性，并系统地研究了H键，溶剂相互作用以及使用良好的模型复合物和蛋白质以及与DFT钙化的实验结果相结合的围绕这些和其他簇围绕这些和其他簇的介电场的影响。 我们还开发了Mo（Tris）二硫烯烯中的键合/几何结构相关性，以及酶和模型的DMSO还原酶家族中的Oxo Trasnsfer机理。 在此提案中，我们计划扩展这种方法，并将其与互补光谱镜结合使用，以研究多种Fe-S系统，例如SAM与丙酮酸裂解酶中Fe4S4簇的相互作用，激活酶； muty-来自大肠杆菌的DNA糖基酶； Fe2S2蛋白与？9去饱和酶结合； Cys-> Ser突变对铁硫簇中电子离域化的影响。 我们还打算研究一系列对亚硫酸盐氧化酶家族态的模拟的Mo单氧和氧化物Bis（二硫代）复合物。 具体的目的是定义酶的电子结构和建模复合物，并了解酶促反应的结构和功能之间的相关性。