STRUCTURAL STUDIES OF TRANSMEMBRANE SIGNALING COMPLEXES AND NOVEL THERAPEUTIC AG

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这些研究集中在疾病进展所需的生理性瞬时跨膜复合体和治疗感染的新疗法上。这两个研究领域各包括三个子项目。我们的第一个重点是跨膜复合体。看似不同的信号蛋白在膜上形成复合体，但很可能共享由构象变化、静电-ICS或动力学变化所介导的最重要的信号机制。我们的研究使用了几个模型系统。确定跨膜信号复合体的结构是结构生物学的前沿。初始晶体的衍射率很低，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治疗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性化合物的酶的结构，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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.