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: 8169978
• 负责人: BRITT HEDMAN
• 金额: $ 1.05万
• 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/8169978
• 关键词: Active Sites; Binding; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupling; Cytochrome P450; Ferredoxin; Funding; Grant; Heme Iron; Hydrogen Bonding; Institution; Investigation; Ligands; Metals; Methodology; Methods; Modeling; Mononuclear; Mutation; Nature; Nitrogenase; Oxidation-Reduction; Property; Proteins; Relative (related person); Research; Research Personnel; Resources; Series; Solvents; Source; Sulfides; United States National Institutes of Health; electronic structure; greigite; high potential iron-sulfur protein; nitrile hydratase; oxidation; protein complex; superoxide reductase

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. 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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 配体K-边缘XAS是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。我们先前的结果表明，将局部降低的Fe2S2群集的2-S-硫化物桥更改为�-3-S-硫化物桥，可降低抗有效耦合的相互作用，从而导致Fe3S4和Fe4s4簇中的DELAICAL耦合相互作用。我们发现，相对于模型，所有蛋白质活性点的Fe-S键共价均显着降低，这可以归因于蛋白质中的H键。特别是，HIPIP中四核[Fe4S4]簇的共价与铁氧还蛋白中的共价差异很大。该方法已扩展以定义二硫醇配体在确定经典一系列Ni-二二烯烯型复合物的氧化还原特性时的非自然性质。我们计划评估HIPIP和铁蛋白之间差异的一般性，并系统地研究使用特征良好的模型复合物和蛋白质在这些簇周围改变字典场的H键，溶剂相互作用以及效果的影响。我们将在[FE3S4]簇上使用当前的结果来了解[MFE3S4]复合物的电子结构，这是用于异核簇的活性位点的模型，包括硝基酶，CODH等。Cys-> ser突变对单核，Binclear，Binclear和Tetranuclear Clusters电子结构的影响。将使用S K-EDGE研究超氧化物还原和氮化液酶的非血红素铁活性位点，以了解活性位点中存在的Fe-S键的氧化水平及其对调整反应性的贡献。我们还将探索P450类型的活性位点以及底物结合对Fe-S键的影响。