BIOLOGICAL ELECTRON TRANSFER

描述：(逐字摘自申请者的摘要)这里提出的研究 有两个长期目标。第一个是了解电子是如何 在具有高度特异性的生物系统中，通过 适当的途径和与新陈代谢一致的速率 要求。第二个是了解蛋白质结构是如何维持其 溶液中与生理相关的三级结构及其作用 耦合的动态过程。为了实现这些目标，各种方法 被使用，主要集中在c型细胞色素，它被开发为 具有良好特征的模型系统。因此，电子转移的动力学研究 和蛋白质动力学与结构分析相结合(x射线 结晶学、核磁共振和建模)、热力学、定点突变、 如果合适的话，还有遗传学。提出了四个具体目标。I.定义 细胞色素上的表面域负责同时 在不同的代谢途径中的识别和特异性。2.澄清 负责进化保守运动的分子过程 细胞色素分子和这些动态过程的生物学作用。3. 确定控制其稳定性的化学和结构特征 C型细胞色素，包括但不限于：氢键网络， 结合水、非极性相互作用和配体-金属相互作用的作用。 4.扩大我们对细胞色素在微生物中的不同作用的理解 生理学，以建立进化适应的广度 识别和特异性，从而识别药物的可能靶点 对病原体的干预。这些研究在解决重要问题的同时 在生物电子转移方面，还将提供关于 蛋白质的结构和功能(识别、稳定性、动力学)将是 适用于广泛的生物过程。

Description: (Verbatim from the Applicant's Abstract) The studies proposed here have two long term objectives. The first is to understand how electrons are transferred in biological systems with high specificity, through the appropriate pathways and with rates that are consistent with metabolic requirements. The second is to understand how protein structures maintain their physiologically relevant tertiary structures in solution and the role of coupled dynamic processes. To accomplish these goals, a variety of approaches are used, focused on c-type cytochromes (principally), which are exploited as well characterized model systems. Thus, kinetic studies on electron transfer and protein dynamics are coupled with structural analysis (x-ray crystallography, NMR and modeling), thermodynamics, site directed mutagenesis, and genetics when appropriate. Four specific aims are addressed. I. Defining the surface domains on cytochromes which are responsible for simultaneous recognition and specificity in their various metabolic pathways. 2. Elucidating the molecular processes responsible for evolutionary conserved movements within a cytochrome molecule and the biological role of these dynamic processes. 3. Establishing the chemical and structural features that control the stability of c-type cytochromes, including but not limited to: hydrogen bond networks, the role of bound waters, nonpolar interactions and ligand-metal interactions. 4. Expanding our understanding of the varied roles of cytochromes in microbial physiology in order to establish the breadth of evolutionary adaptations in recognition and specificity and thus to identify possible targets for drug intervention in pathogens. These studies, while addressing important issues in biological electron transfer, will also provide fundamental information on protein structure and function (recognition, stability, dynamics) that will be applicable to a wide range of biological processes.