STRUCTURAL STUDIES OF TRANSMEMBRANE SIGNALING COMPLEXES AND NOVEL THERAPEUTIC AG

跨膜信号复合物和 NOVEL THERAPEUTIC AG 的结构研究

• 批准号: 8362282
• 负责人: T M Iverson
• 金额: $ 0.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362282
• 关键词: Area; Bacterial Infections; Biological Models; Complex; Disease Progression; Feedback; Funding; Grant; HIV Infections; Infection; Mediating; Membrane; National Center for Research Resources; Principal Investigator; Radiation; Research; Research Infrastructure; Resolution; Resources; Signal Transduction; Signaling Protein; Source; Structure; Therapeutic; United States National Institutes of Health; base; chemical reaction; cost; enzyme structure; improved; novel; novel therapeutics; structural biology

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 这些研究重点关注疾病进展所需的生理学瞬时跨膜复合物和治疗感染的新疗法。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。看似不同的信号蛋白跨膜形成复合物，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总体机制。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处于结构生物学的前沿。初始晶体的衍射性能很差，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针对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。