BIOLOGICAL METAL CLUSTERS BIOPHYSICAL & MODEL STUDIES

生物金属簇 生物物理

• 批准号: 6120378
• 负责人: MICHAEL J MARONEY
• 金额: --
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120378
• 关键词: bacteria; biological products; biomedical resource; enzymes; proteins; spectrometry

Enzyme and protein active sites containing two or more interacting metal centers now figure prominently in metallobiochemistry. Systems containing metal clusters composed of Fe atoms (e.g., ferredoxins, sulfite reductase, hemerythrin, tyrosinase, ceruloplasmin, cytochrome oxidase), Mn atoms (photosystem II, catalase), and more than one element, or heteropolynuclear clusters (e.g., nitrogenase-Mo,Fe; cytochrome oxidase-Fe,Cu, hydrogenase and carbon monoxide dehydrogenase- Ni,Fe) have been identified. The ultimate goals of this project are to elucidate the structures of the metal clusters in metalloproteins, to determine the roles these clusters serve in the function of the protein , and to understand how nature designs a cluster for a specific purpose. This knowledge will provide a detailed understanding of biological processes and will aid in the design of pharmaceutical enzyme inhibitors and catalysts for various reactions. During the current report period, we completed studies of the structures of the Ni sites in eleven forms of Chromatium vinosum hydrogenase. These studies lead to three important conclusions related to the enzyme structure and function. First, the Ni-S distances differ by at most ~ 0.15 E, rather than 0.4 E as suggested by crystallographic information. Second, there is an oscillation in the edge energy observed in samples from enzyme in a ready conformation that indicates that the active site has two redox states (oxidized and reduced) and that these states differ by one electron. Last, there is a change in the Ni-Fe distance in the active site from a long distance (ca. 2.8 E) to a short distance (2.5 E) that is correlated with the reduction of the active site. This may be due to the binding of substrate or the loss of a solvent-derived O-donor bridging ligand upon reduction.

含有两个或多个相互作用位点的酶和蛋白质活性位点 金属中心现在在金属生物化学中占有重要地位。 系统 含有由Fe原子组成的金属簇（例如，铁氧还蛋白， 亚硫酸盐还原酶、血红蛋白、酪氨酸酶、铜蓝蛋白、细胞色素 氧化酶），锰原子（光系统II，过氧化氢酶），和一个以上的 元素，或杂多核簇（例如，固氮酶-钼、铁; 细胞色素氧化酶-铁、铜、氢化酶和一氧化碳 脱氢酶- Ni，Fe）的活性。 的最终目标 本项目旨在阐明金属团簇的结构， 金属蛋白，以确定这些集群在 蛋白质的功能，并了解自然如何设计一个 集群用于特定目的。 这些知识将提供一个 详细了解生物过程，并将有助于 用于各种用途的药物酶抑制剂和催化剂的设计 反应. 在本报告所述期间，我们完成了对 葡萄色菌十一种变型的Ni位结构 氢化酶 这些研究得出三个重要结论 与酶的结构和功能有关。 首先，Ni-S 距离最多相差约0.15 E，而不是建议的0.4 E 晶体学信息。 第二，有一个振荡， 在来自酶的样品中观察到的边缘能量， 准备 构象，表明活性位点具有两种氧化还原态 （氧化和还原），这些状态相差一个电子。 最后，活性中心中的Ni-Fe距离从 长距离（长距离） 2.8 E）到短距离（2.5 E），即 与活性位点的减少有关。 这可能是由于 底物的结合或溶剂衍生的O-供体的损失 桥连配体还原。