BIOLOGICAL ELECTRON TRANSFER

生物电子转移

• 批准号: 7149011
• 负责人: MICHAEL Anthony CUSANOVICH
• 金额: $ 32.09万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-03-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149011
• 关键词: Rhodospirillales; bacterial genetics; chemical kinetics; cytochrome b; cytochrome c; electron transport; fusion gene; gene expression; genetic regulation; hemoprotein; microarray technology; molecular assembly /self assembly; molecular dynamics; oxidation reduction reaction; photosynthetic reaction centers; protein binding; protein metabolism; protein protein interaction; protein structure function; surface plasmon resonance

DESCRIPTION (provided by applicant): Transient protein-protein interactions modulate a very large range of biochemical processes. The importance of understanding protein-protein interactions goes well beyond fundamental basic science, as these interactions may well be important drug targets in addition to enzyme active sites, especially in relation to infectious diseases. The studies of protein-protein interactions proposed here address two long-term goals. First, to determine the basic structural, dynamic and chemical motifs that are central to biological recognition and specificity in protein-protein interactions. Our approach toward accomplishing this goal tests a model for the interaction of c-type cytochromes with their physiologically relevant electron donors and acceptors, and takes particular advantage of a new technology, plasmon waveguide resonance. This technology permits studies under conditions which mimic the in vivo conditions. We believe that the results of the proposed studies will provide fundamental mechanistic information that is broadly applicable to other, in many cases more complex or less tractable systems. Second, taking advantage of the availability of the Rhodobacter sphaeroides genome sequence and utilizing genomic based technologies (microarray and lacZ fusions) we will determine the regulation and expression of the twenty six c-type cytochromes in the Rhodobacter sphaeroides genome. The proposed studies will identify reaction partners and pathways previously unknown and greatly expand our understanding of the diversity of mechanisms used to control recognition and specificity in metabolic function. The growing resistance to antibiotics makes it imperative that we better understand microbial physiology/biochemistry in order to develop novel strategies to address bacterial infections. Thus, currently uncharacterized pathways not used by mammals may eventually be exploited for drug intervention and/or for environmental bioremediation.

描述（由申请人提供）：瞬时蛋白质-蛋白质相互作用调节非常大范围的生化过程。理解蛋白质-蛋白质相互作用的重要性远远超出了基础科学，因为这些相互作用很可能是除了酶活性位点之外的重要药物靶点，特别是与感染性疾病有关的药物靶点。这里提出的蛋白质-蛋白质相互作用的研究解决了两个长期目标。首先，确定蛋白质-蛋白质相互作用中生物识别和特异性的基本结构，动力学和化学基序。我们的方法实现这一目标的测试模型的c型细胞色素与他们的生理相关的电子供体和受体的相互作用，并特别利用一种新技术，等离子体波导共振。该技术允许在模拟体内条件的条件下进行研究。我们相信，所提出的研究结果将提供基本的机械信息，广泛适用于其他，在许多情况下更复杂或更难处理的系统。其次，利用球形红细菌基因组序列的可用性和利用基于基因组的技术（微阵列和lacZ融合），我们将确定球形红细菌基因组中26个C型细胞色素的调节和表达。拟议的研究将确定以前未知的反应伙伴和途径，并大大扩展我们对用于控制代谢功能识别和特异性的机制多样性的理解。对抗生素日益增长的耐药性使我们必须更好地了解微生物生理学/生物化学，以便开发新的策略来解决细菌感染。因此，目前未被哺乳动物使用的未表征的途径最终可能被用于药物干预和/或环境生物修复。