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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 小的惰性分子如二氢、二氮、碳氧化物的生物活化在环境压力和温度下发生，并且涉及嵌入蛋白质基质中的复杂无机结构。氢化酶是金属酶，其中二氢还原或氧化发生在具有氰化物/羰基和桥接硫醇盐配体的独特的六铁簇上。这些酶在包括人类胃细菌在内的缺氧微生物的体内平衡中具有生理作用。它们与其他小分子活化过程如固氮酶和产甲烷酶偶联作为电子/质子或二氢源。这些生物无机过程的机制研究可以提供进一步了解的作用，无机化合物在酶系统中，并允许设计新的生物无机化合物与工业的重要性。在没有充分利用酶的催化活性的情况下，已经制备了各种各样的氢化酶活性位点的结构类似的双氢邻苯二甲酸酯。系统的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。功能上类似的双氢子，但与活性位点相比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，这些因素使得无机合成子能够将电子和质子结合为二氢或反之亦然。金属蛋白质的直接研究将最终提供电子结构的描述，从而提供化学机制所需的实验波函数。将研究来自几种生物的氢化酶，以研究微生物环境对活性位点结构的依赖性，并与它们作为氢吸收或进化酶的不同作用相关联。

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.