BIOLOGICAL METAL CLUSTERS--BIOPHYSICAL & MODEL STUDIES

生物金属簇--生物物理

• 批准号: 3466502
• 负责人: MICHAEL J MARONEY
• 金额: $ 11.34万
• 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/3466502
• 关键词: enzyme structure; hemerythrin; hydrogenase; iron; metal complex; metalloenzyme; metalloproteins; 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.

许多氢化酶和CO-脱氢酶的活性位点 已被证明含有磁性相互作用的Fe，S 团簇和顺磁Ni中心。 这些酶用于 氧化分子氢（或还原氢离子）， 将一氧化碳氧化成二氧化碳， 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位点结构或机制： 其中金属簇执行所需的氧化还原催化。 氢化酶和CO脱氢酶的合成模型 活性位点和拟议的中间体的定义，和研究 它们的光谱和物理特性，特别是EPR 光谱和氧化还原化学，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光谱研究的简单 光合紫硫细菌的氢化酶 葡萄色霉菌和玫瑰柄硫孢菌，结合 与EXAFS研究的活性位点模型，预计将 有助于蛋白质活性位点的表征。 双核铁簇合物与O-供体桥联基团构成 另一类蛋白质活性位点参与的建议， 调查事务所 蛋白质被认为含有活性位点， 该生物金属簇包括：血红蛋白、子宫铁蛋白 和其它紫色酸性磷酸酶，核糖核苷酸还原酶，和 甲烷单加氧酶 这些蛋白质具有不同的功能： 氧转运，磷代谢调节，转化 核糖核苷酸到脱氧核糖核苷酸（DNA的关键步骤 合成）和甲烷氧化成甲醇。 在每一种情况下， 活性位点金属簇的混合价形式似乎是 参与催化或活性部位的构建。 以三氟氯氰菊酯为原型， 研究重点是可能的价间跃迁和配体- 提出了混合价团簇中的场跃迁， 定义电子传递的作用和连接的变化， 氧结合机制，以及照亮类似 其他双核活性部位的性质。 最终， 金属配体在定制双核铁簇中， 将定义特定的生物学功能。