INVESTIGATION OF ELECTRONIC STRUCTURES OF FE-S AND MO-S ACTIVE SITES AND THEIR R

FE-S和Mo-S活性位点的电子结构及其R的研究

• 批准号: 8362082
• 负责人: BRITT HEDMAN
• 金额: $ 0.47万
• 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/8362082
• 关键词: Active Sites; Binding; Complex; Coupling; Cytochrome P450; Ferredoxin; Funding; Grant; Hydrogen Bonding; Investigation; Iron; Ligands; Metals; Methodology; Methods; Modeling; Mononuclear; Mutation; National Center for Research Resources; Nature; Nitrogenase; Oxidation-Reduction; Principal Investigator; Property; Proteins; Radiation; Relative (related person); Research; Research Infrastructure; Resources; Series; Solvents; Source; Sulfides; United States National Institutes of Health; cost; electronic structure; greigite; nitrile hydratase; oxidation; protein complex; structural biology; superoxide reductase

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 is 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 Cu-S and Fe-S clusters. Our previous results showed that changing a ¿2-S-sulfide bridge of a localized reduced Fe2S2 cluster to a ¿-3-S-sulfide bridge reduces the anti-ferromagnetic coupling interaction leading to delocalized ground states in Fe3S4 and Fe4S4 clusters. We have found that there is a significant reduction of Fe-S bond covalency in all the protein active-sites relative to the models, which can be attributed to H-bonding in the protein. Particularly, the covalency of the tetranuclear [Fe4S4] cluster in HiPIP was very different than that in ferredoxin. The method has been extended to define the non-innocent nature of the dithiolene ligands in determining the redox properties of a classic series of Ni-dithiolene complexes. We plan to evaluate the generality of the difference between HiPIPs and ferredoxins and systematically study the effect of H-bonding, solvent interaction and effect of changing dielectric field around these clusters using well-characterized model complexes and proteins. We will use current results on [Fe3S4] clusters to understand the electronic structures of [MFe3S4] complexes which are models for the active sites of heteronuclear clusters including nitrogenase, CODH, etc. The effects of Cys->Ser mutation on the electronic structures of mononuclear, binuclear and tetranuclear clusters will be evaluated. The non-heme iron active sites of superoxide reductase and nitrile hydratase will be studied using S K-edge to understand the oxidation level of the Fe-S bonds present in the active site and their contribution to tuning reactivity. We will also explore P450 type active sites and the effect of substrate binding on the Fe-S bond.

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 该子项目的主要支持。 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 来源的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。 配体 K 边缘 XAS 是配体金属键合的直接探针，我们开发了这种方法来研究 Cu-S 和 Fe-S 簇的模型复合物和蛋白质活性位点的电子结构。局部还原 Fe2S2 簇的 2-S-硫桥至 ¿ -3-S-硫桥减少了反铁磁耦合相互作用，导致 Fe3S4 和 Fe4S4 簇中的离域基态我们发现，相对于所有蛋白质活性位点，Fe-S 键共价键显着减少。模型中，这可归因于蛋白质中的氢键，特别是 HiPIP 中四核 [Fe4S4] 簇的共价性与 HiPIP 中的有很大不同。该方法已扩展到定义二硫烯配体的非无害性质，以确定一系列经典的 Ni-二硫烯复合物的氧化还原性质。我们计划评估 HiPIP 和铁氧还蛋白之间差异的普遍性，并系统地研究它们。我们将使用 [Fe3S4] 簇的当前结果。了解[MFe3S4]复合物的电子结构，该复合物是异核簇活性位点的模型，包括固氮酶、CODH等。将评估Cys->Ser突变对单核、双核和四核簇电子结构的影响。将使用 S K-edge 研究超氧化物还原酶和腈水合酶的非血红素铁活性位点，以了解活性中存在的 Fe-S 键的氧化水平我们还将探讨 P450 型活性位点以及底物结合对 Fe-S 键的影响。