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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 二氢、二氮、一氧化碳等惰性小分子的生物活化在常压和温度下发生，涉及嵌入蛋白质基质的错综复杂的无机结构。氢酶是金属酶，其中二氢还原或氧化发生在一个独特的六铁簇上，带有氰化物/羰基和桥联的硫酸盐配体。这些酶在人体内包括胃细菌在内的缺氧微生物的动态平衡中起着生理作用。它们与其他小分子激活过程，如固氮酶和产甲烷酶偶联，作为电子/质子或双氢源。对这些生物无机过程的机理研究可以进一步了解无机化合物在酶系统中的作用，并有助于设计具有工业意义的新型合成子。氢酶活性部位的各种结构相似的合成子已经被制备出来，而没有充分利用该酶的催化活性。对这些合成子的系统光谱研究可以为活性中心的电子结构和几何结构提供坚实的基础。生物样品中的蛋白质环境可以被认为是对这些结构的扰动，以实现催化活性。功能相似的合成子，但与活性中心具有不同的配体环境，可用于定义关键的电子和几何结构因素，使无机合成子能够将电子和质子结合成二氢，反之亦然。直接的金属蛋白研究最终将提供化学机制所需的电子结构描述和实验波函数。将对几种生物的氢酶进行研究，以了解微生物环境对活性部位结构的依赖，以及它们作为吸氢或放氢酶的不同作用。

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.