Biosynthesis and Reactivity of the Active Site of the FeFe Hydrogenases

FeFe 氢化酶活性位点的生物合成和反应性

• 批准号: 10693280
• 负责人: Thomas Rauchfuss
• 金额: $ 31.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693280
• 关键词: Active Sites; Address; Alkylation; Ally; Amino Acids; Anabolism; Archaea; Bacteria; Binding; Biogenesis; Carbon Dioxide; Cells; Chemicals; Chemistry; Complex; Coupling; Cysteine; Cystine; Development; Environment; Enzymes; Evaluation; Glycine Hydroxymethyltransferase; Grant; Hand; Human; Hydrogen; Hydrogenase; Iron; Knowledge; Learning; Maps; Mediating; Methods; Molecular; Nature; Organism; Oxidation-Reduction; Pathogenicity; Pathway interactions; Preparation; Production; Protons; Reaction; Reagent; Role; Route; Site; Source; Structure; Sulfur; Testing; abstracting; adduct; analog; biophysical analysis; catalyst; chemical reaction; cofactor; dehydrogenation; design; dimer; inhibitor; interest; monomer; novel; oxidation; pathogen; programs; stem; theories; thioether; tool

Project Summary Hydrogenase enzymes are pervasive, being found in bacteria, archaea, and some higher organisms. These enzymes are hosted by some pathogens, often in anaerobic environments including the human gut. The hydrogenases mediate the most fundamental chemical reaction: the interconversion of H2 with protons and reducing equivalents. The enzymes are structurally exceptional with an array of distinctive cofactors, especially the site of H2 binding and release. Interest in such enzymes stems from three angles: the possibility that some pathogens could be controlled rationally, the excitement about their unusual structures, and the commercial implications of hydrogen production/oxidation in the context of fuel cells. Two major classes of hydrogenases exist, [NiFe]- and [FeFe]-hydrogenases. This project is almost exclusively focused on the latter. More specifically, this project aims to elucidate the biosynthesis of the active site of [FeFe] enzymes, the faster hydrogenase and the one most amenable to development for other applications. This project is timely because we have just defined the sequence by which the three maturase enzymes build the active site. In parallel with their unusual structures, the construction (biosynthesis) of the active site proceeds unusually. The first subproject aims to make the first Fe-containing intermediate, "Compound B". The next two projects tackle how B is converted to an inorganic Fe-S-CN-CO monomer. The fourth project examines the coupling of this monomer to give an inorganic dimer. The final and fifth project examines the retrofitting of this Fe2 entity with an organic cofactor. In this program collateral projects address allied themes of still broader interest. One involves expanding our knowledge of iron complexes of amino acids. Another contributes to the biosynthesis of [NiFe]-hydrogenases. One spin-off project critically examines the premises of the Iron-Sulfur Theory of the origin of life by examination of the first Fe-S-CN-CO complexes.

项目摘要 氢化酶是普遍存在的，存在于细菌、古生菌和一些 更高的生物。这些酶由一些病原体宿主，通常在厌氧环境中， 包括人类肠道在内的环境。氢化酶介导的 基本化学反应：H2与质子的相互转化， 等价物这些酶在结构上是特殊的，具有一系列独特的 辅因子，特别是H2结合和释放的位点。对这些酶的兴趣源于 从合理控制某些病原体的可能性、 他们对氢原子不同寻常的结构以及氢原子的商业意义感到兴奋 在燃料电池的情况下，生产/氧化。 存在两种主要的氢化酶，[NiFe]-和[FeFe]-氢化酶。这 该项目几乎完全集中在后者。更具体地说，该项目旨在 阐明[FeFe]酶的活性位点的生物合成，更快的氢化酶 也是最适合开发用于其他应用的方法。这个项目是及时的 因为我们刚刚定义了三种成熟酶的序列 活性部位。与其不寻常的结构平行，结构（生物合成） 活动地点的活动异常。 第一个子项目旨在制备第一种含铁中间体“化合物B”。 接下来的两个项目将研究B如何转化为无机Fe-S-CN-CO单体。 第四个项目研究了这种单体的偶联，得到一个无机二聚体。 最后一个也是第五个项目检查了这个铁实体的改造与有机 辅因子 在这个计划中，附属项目涉及更广泛兴趣的相关主题。一 涉及扩展我们对氨基酸铁复合物的知识。另一 有助于[NiFe]-氢化酶的生物合成。一个附带项目至关重要 通过检查生命起源的铁硫理论的前提， 第一种Fe-S-CN-CO络合物。

项目成果

Multicopper models for the laccase active site: effect of nuclearity on electrocatalytic oxygen reduction.

• DOI: 10.1021/ic501080c
• 发表时间: 2014-07
• 期刊: Inorganic chemistry
• 影响因子: 4.6
• 作者: Edmund C. M. Tse;D. Schilter;Danielle L. Gray;T. Rauchfuss;A. Gewirth

Direct Observation of an Iron-Bound Terminal Hydride in [FeFe]-Hydrogenase by Nuclear Resonance Vibrational Spectroscopy.

• DOI: 10.1021/jacs.7b00686
• 发表时间: 2017-03-29
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Reijerse EJ;Pham CC;Pelmenschikov V;Gilbert-Wilson R;Adamska-Venkatesh A;Siebel JF;Gee LB;Yoda Y;Tamasaku K;Lubitz W;Rauchfuss TB;Cramer SP
• 通讯作者: Cramer SP

Aza- and oxadithiolates are probable proton relays in functional models for the [FeFe]-hydrogenases.

• DOI: 10.1021/ja8057666
• 发表时间: 2008-12-17
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Barton, Bryan E.;Olsen, Matthew T.;Rauchfuss, Thomas B.
• 通讯作者: Rauchfuss, Thomas B.

Rational Synthesis of the Carbonyl(perthiolato)diiron [Fe2(S3CPh2)(CO)6] and Related Complexes.

羰基(全硫醇)二铁[Fe2(S3CPh2)(CO)6]及相关配合物的合理合成。

• DOI: 10.1002/ejic.201600366
• 发表时间: 2016
• 期刊: European journal of inorganic chemistry
• 影响因子: 2.3
• 作者: Zhao,Peihua;Gray,DanielleL;Rauchfuss,ThomasB
• 通讯作者: Rauchfuss,ThomasB

The iron-site structure of [Fe]-hydrogenase and model systems: an X-ray absorption near edge spectroscopy study.

• DOI: 10.1039/b922557a
• 发表时间: 2010-03-28
• 期刊: Dalton transactions (Cambridge, England : 2003)
• 作者: Salomone-Stagni M;Stellato F;Whaley CM;Vogt S;Morante S;Shima S;Rauchfuss TB;Meyer-Klaucke W
• 通讯作者: Meyer-Klaucke W