BIOLOGICAL METAL CLUSTERS--BIOPHYSICAL & MODEL STUDIES

生物金属簇--生物物理

• 批准号: 3466505
• 负责人: MICHAEL J MARONEY
• 金额: $ 10.34万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3466505
• 关键词: catalyst; electron probe spectrometry; electron transport; enzyme model; enzyme structure; hemerythrin; hydrogenase; iron; metal complex; metalloenzyme; metalloproteins; molecular site; nickel; oxidation reduction reaction; sulfur compounds

The active sites of many hydrogenases and CO-dehydrogenases have been shown to contain magnetically interacting Fe, S clusters and paramagnetic Ni centers. These enzymes serve to oxidize molecular hydrogen (or reduce hydrogen ions) and to oxidize carbon monoxide to carbon dioxide and thus serve key roles in the bioenergetics of certain microorganisms. Very little is known about the active site structure or the mechanism by which the metal clusters perform the required redox catalysis. Synthetic models for the hydrogenase and CO dehydrogenase active sites and proposed intermediates are defined, and the study of their spectroscopic and physical properties, particularly epr spectra and redox chemistry, is proposed as a means for elucidating the structure and function of these biological metal clusters. In addition, EXAFS spectral studies on simple hydrogenases from the photosynthetic purple sulfur bacteria Chromatium vinosum and Thiocapsa roseoperscina, in conjunction with EXAFS studies of the active site models, are expected to contribute to the characterization of the protein active sites. Binuclear iron clusters with O-donor bridging groups constitute another class of protein active sites involved in the proposed investigations. Proteins believed to contain active sites featuring this biological metal cluster include: hemerythrin, uteroferrin and other purple acid phosphatases, ribonucleotide reductase, and methane monooxygenase. The proteins serve diverse functions: oxygen transport, regulation of phosphate metabolism, conversion of ribonucleotides to deoxyribonucleotides ( a key step in DNA synthesis), and oxidation of methane to methanol. In each case, mixed-valent forms of the active site metal cluster appear to be involved in the catalysis or in the construction of the active site. Using hemerythrin as a prototype, electronic absorption spectral studies focusing on possible intervalence transitions and on ligand- field transitions in mixed-valent clusters are proposed in order to define the role of electron transport and changes in ligation in the oxygen-binding mechanism, as well as illuminate similar properties in other binuclear active sites. Ultimately, the role of the metal ligands in tailoring the binuclear iron clusters to specific biological functions will be defined.

多种氢酶和共脱氢酶的活性部位 已经被证明含有磁性相互作用的铁，S 团簇和顺磁镍中心。这些酶可以用来 氧化分子氢(或还原氢离子)和 将一氧化碳氧化成二氧化碳，从而成为关键 在某些微生物的生物能量学中的作用。很少 通过以下方式了解活性部位的结构或机制 其中金属团簇执行所需的氧化还原催化。 氢酶和CO脱氢酶的合成模型 定义了活性中心和建议的中间体，并研究了 它们的光谱和物理性质，特别是EPR 光谱和氧化还原化学，被提出作为一种手段 阐明这些生物金属的结构和功能 集群。此外，EXAFS光谱分析还研究了 光合作用紫硫细菌的氢酶 棕色染色霉属和玫瑰色囊霉属 随着EXAFS对活跃站点模型的研究，预计 有助于确定蛋白质活性部位的特性。 含O-施主桥基的双核铁团簇构成 另一类蛋白质活性位点参与了建议的 调查。据信含有活性位点的蛋白质具有以下特征 该生物金属簇包括：三氯氰菊酯、子宫铁蛋白 和其他紫色酸性磷酸酶、核苷酸还原酶和 甲烷单加氧酶。这些蛋白质具有不同的功能： 氧运输、磷酸盐代谢调节、转化 从核糖核苷酸到脱氧核糖核苷酸(DNA的关键一步 合成)，以及甲烷氧化成甲醇。在每一种情况下， 活性中心金属簇的混合价形式似乎是 参与催化或活性部位的构建。 以三氯氰菊酯为原型，电子吸收光谱 重点研究了可能的价间跃迁和配体- 提出了混合价团簇中场跃迁的概念 明确电子传递的作用和在结扎过程中的变化 氧结合机理，以及照亮相似 其他双核活性中心的性质。归根结底， 双核铁团簇裁剪中的金属配体 具体的生物功能将被定义。