BIOLOGICAL ELECTRON TRANSFER

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，因为除了酶活性位点之外，这些相互作用很可能是重要的药物靶点，特别是与传染病有关的药物靶点。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，确定蛋白质相互作用中生物识别和特异性的基本结构、动态和化学基序。我们实现这一目标的方法测试了c型细胞色素与其生理相关的电子供体和受体相互作用的模型，并特别利用了一种新技术，等离子体波导共振。这项技术允许在模拟体内条件的条件下进行研究。我们认为，拟议研究的结果将提供基本的机制信息，广泛适用于其他，在许多情况下更复杂或更不易处理的系统。其次，利用球形红杆菌基因组序列的可用性，利用基因组技术（微阵列和lacZ融合），我们将确定球形红杆菌基因组中26个c型细胞色素的调控和表达。拟议的研究将确定以前未知的反应伙伴和途径，并极大地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。抗生素耐药性的增长使得我们必须更好地了解微生物生理学/生物化学，以便制定新的策略来解决细菌感染。因此，哺乳动物目前未使用的未表征途径可能最终被用于药物干预和/或环境生物修复。

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.