REACTION MECHANISM OF MYOCARDIAL UBIQUINONE-PROTEINS

心肌泛醌蛋白的反应机制

• 批准号: 3278552
• 负责人: CHANG-AN YU
• 金额: $ 18.02万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3278552
• 关键词: NADPH cytochrome c2 reductase; analytical method; binding proteins; bioenergetics; chemical binding; chemical reaction; chemical synthesis; cow; cytochrome b; cytochrome c; electron spin resonance spectroscopy; electron transport; enzyme complex; enzyme structure; laboratory mouse; laboratory rabbit; mitochondria; myocardium; phospholipids; physical separation; protein sequence; protein structure; succinate dehydrogenase; ubiquinone

Our objective is to continue elucidation of the molecular reaction mechanisms of the ubiquinone (Q)-mediated mitochondrial electron transfer and energy conservation through study of the two Q-binding protein systems, QPs and QPc, in succinate-Q and ubiquinol-cytochrome c reductase, respectively. The involvement of specific Q-binding proteins (sites) in the mitochondrial electron transfer system has been established and isolated or identified during past support periods. The next step will be the isolation and characterization of active Q-binding proteins, and elucidation of the structure of the Q-binding sites. Multiple approaches will be taken to study the Q-binding sites and Q:protein interaction in both ubiquinol-cytochrome c reductase and succinate-Q reductase. These include: (1) isolation and sequencing of the Q-binding peptides from the isolated Q-binding proteins, (2) organic synthesis of Q derivatives with different functional (electron donating or accepting) properties, and Q derivatives with detectable groups for studying the Q:protein interaction, (3) chemical modification of the Q-binding site, and (4) immunological characterization of the Q-binding sites and proton translocation sites (domains) of Q-binding proteins. The interaction between succinate-Q reductase and ubiquinol cytochrome reductase will be studied by chemical and photoaffinity double labeling technique and by differential scanning calorimetry. The possible involvement of free Q in electron transfer and proton translocation will also be examined. The acceptance of the principle of the chemiosmotic energy coupling hypothesis has given Q a central role in bioenergetics. Success in the proposed research will increase our knowledge of electron transfer and proton translocation reactions. In addition, elucidation of the Q-binding site and Q:protein interaction will provide information crucial to understanding the mechanism of the generation of superoxide, and thus be useful in future investigations of cytotoxicity and aging.

我们的目标是继续阐明分子反应 泛氨基酮（Q）介导的线粒体电子转移的机理 通过研究两个Q结合蛋白系统的能源保护， QPS和QPC，在琥珀酸酯和泛素醇 - 卵形c还原酶中， 分别。 特定Q结合蛋白（位点）参与 线粒体电子传输系统已建立，并且 在过去的支持期间被隔离或确定。 下一步将是 活性Q结合蛋白的隔离和表征，以及 阐明Q结合位点的结构。 多种方法 将采取研究Q结合位点和Q：蛋白质相互作用 泛素醇 - 卵色素C还原酶和琥珀酸Q还原酶。 这些 包括：（1）从Q结合肽的隔离和测序 分离的Q结合蛋白，（2）与Q衍生物合成的有机合成 不同的功能（电子捐赠或接受）特性，Q 具有可检测组的衍生物用于研究Q：蛋白质相互作用， （3）Q结合位点的化学修饰，（4）免疫学 Q结合位点和质子易位位点的表征 Q结合蛋白的（域）。 琥珀酸Q之间的相互作用 还将通过化学研究还原酶和泛醇细胞色素还原酶 和光性双重标签技术以及通过差速器扫描 量热法。 游离Q可能参与电子传输和 还将检查质子易位。 接受化学能量偶联原理的接受 假设在生物能学中赋予了Q。 成功 拟议的研究将增加我们对电子转移的了解，并 质子易位反应。 另外，阐明Q结合 站点和Q：蛋白质相互作用将为您提供至关重要的信息 了解超氧化物产生的机制，从而成为 对未来的细胞毒性和衰老研究有用。