MOLECULAR MECHANISM OF SMALL MOLECULE ACTIVATION IN BIOLOGY: HYDROGENASES AND RE

生物学中小分子激活的分子机制：加氢酶和稀土

• 批准号: 7598037
• 负责人: Robert Karoly Szilagyi
• 金额: $ 0.79万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598037
• 关键词: Active Sites; Bacteria; Biological; Biology; Chemicals; Classification; Computer Retrieval of Information on Scientific Projects Database; Coupled; Dependence; Electronics; Electrons; Environment; Enzymes; Evolution; Funding; Grant; Homeostasis; Human; Hydrogen; Hydrogenase; Institution; Investigation; Iron; Ligands; Metalloproteins; Molecular; Nitrogenase; Organism; Physiological; Process; Proteins; Protons; Research; Research Personnel; Resources; Role; Sampling; Solid; Source; Stomach; Structure; System; Temperature; United States National Institutes of Health; base; design; enzyme activity; mesoxalonitrile; metalloenzyme; microbial; microorganism; novel; oxidation; pressure; small molecule

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. Biological activation of small, inert molecules such as dihydrogen, dinitrogen, carbonoxides, occurs at ambient pressure and temperature and involves intricate inorganic structures embedded into the protein matrix. The hydrogenases are metalloenzymes, where the dihydrogen reduction or oxidation takes place on a unique six-iron cluster with cyanide/carbonyl and bridging thiolate ligands. These enzymes have physiological role in the homeostasis of anoxic microorganism including gastric bacteria in humans. They are coupled to other small molecule activation processes such as nitrogenase and methanogenic enzymes as electron/proton or dihydrogen sources. Mechanistic investigation of these bioinorganic processes can provide further understanding of the role of inorganic compounds in enzymatic systems and would allow for design of novel synthons with industrial importance. A wide variety of structurally analogous synthons for the hydrogenase active site has already been prepared without the full benefit of the catalytic activity of the enzyme. Systematic spectroscopic studies of these synthons can provide a solid basis for the electronic and geometric structures of the active sites. The protein environment in biological samples can be considered as a perturbation to these structures to achieve the catalytic activity. Functionally analogous synthons, but with different ligand environment than the active site, are available to define the key electronic and geometric structural factors what makes an inorganic synthon capable of combining electrons and protons to dihydrogen or vice versa. The direct metalloprotein studies will ultimately provide the electronic structure description and hence the experimental wave function needed for the chemical mechanism. Hydrogenases from several organisms will be studied in order to investigate the microbial environment dependence on the active site structure and correlate with their different roles as hydrogen up-take or evolution enzymes.

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