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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。