STRUCTURAL STUDIES OF TRANSMEMBRANE SIGNALING COMPLEXES AND NOVEL THERAPEUTIC AG

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这些研究集中在疾病进展和治疗感染的新疗法所需的生理学瞬时跨膜复合物。这两个研究领域各包含三个子项目。我们的第一个重点是跨膜复合物。表面上不同的信号蛋白形成跨膜复合物，但可能共享由构象变化、静电或动力学变化介导的信号传导的过度介导机制。我们的研究使用了几个模型系统。跨膜信号复合物结构的确定是结构生物学的前沿。初始晶体的衍射性能较差，需要基于衍射的反馈来将衍射极限提高到合理的分辨率。我们的第二个重点是开发细菌和艾滋病毒感染的新疗法。在这里，我们正在确定合成治疗化合物的酶的结构，以提高或调整化学反应的效率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. These studies focus on physiologically transient transmembrane complexes that are required for disease progression and novel therapies to treat infections. These two research areas each encompass three sub-projects. Our first focus is on transmembrane complexes. Seemingly disparate signaling proteins form complexes across the membrane, but likely share over-arching mechanisms of signaling mediated by conformational changes, electrostat-ics, or changes in dynamics. Our studies use several model systems. Determination of the structures of transmembrane signaling complexes is at the cutting edge of structural biology. The initial crystals diffract poorly and require diffraction-based feedback to improve the diffraction limit to reasonable resolution. Our second focus is on developing novel therapies for bacterial and HIV infections. Here, we are determining the structures of enzymes that synthesize therapeutic compounds in order to improve or tune the efficiency of the chemical reaction.