FRAGMENT BASED DRUG DISCOVERY TARGETING HIV PROTEASE

针对 HIV 蛋白酶的基于片段的药物发现

• 批准号: 8362285
• 负责人: Charles David Stout
• 金额: $ 2.71万
• 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/8362285
• 关键词: Adhesions; Anti-Bacterial Agents; Bacteriophages; Biochemistry; Data; Electron Microscopy; Filament; Funding; Grant; HIV Protease; Intervention; Mediating; Membrane; Molecular Machines; Molecular Motors; National Center for Research Resources; Pathogenesis; Pilum; Play; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Role; Source; Structure; Surface; System; United States National Institutes of Health; Virulence; Virulence Factors; Work; base; cell motility; cost; design; drug discovery; interest; pathogen; solid state nuclear magnetic resonance; 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. Type IV pili (T4P) are key virulence factors for many bacterial pathogens, mediating a broad range of functions including surface motility, microcolony formation, adhesion, phage attachment and natural transformation. Type IV pili are of great scientific interest due to the central role these filaments play in bacterial pathogenesis and for their potential as targets for antibacterial interventions. Furthermore, from a biophysical standpoint, the pilus assembly apparatus represents a remarkable and unique molecular motor. We are working to solve the crystal structures of the components of the inner membrane platform of the Type IV pilus assembly apparatus. These data will be combined with structural data obtained from solid state NMR, electron microscopy, mutational analysis and biochemistry to obtain a detailed understanding of this critical molecular machine. This work will likely contribute to the design of new antibacterial therapies and to our understanding of another critical bacterial virulence system, the Type 2 secretion, which is highly similar to Type IV pilus system.

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。 IV型皮利（T4 P）是许多细菌病原体的关键毒力因子，介导广泛的功能，包括表面运动、小菌落形成、粘附、噬菌体附着和自然转化。IV型皮利具有很大的科学意义，因为这些丝状体在细菌发病机制中起着中心作用，并且它们具有作为抗菌干预靶点的潜力。此外，从生物物理学的角度来看，菌毛组装装置代表了一个显着的和独特的分子马达。我们正在努力解决IV型菌毛组装装置的内膜平台组件的晶体结构。这些数据将与从固态NMR，电子显微镜，突变分析和生物化学获得的结构数据相结合，以获得对这一关键分子机器的详细了解。这项工作可能有助于设计新的抗菌治疗方法，并有助于我们了解另一个关键的细菌毒力系统，即与IV型菌毛系统高度相似的2型分泌。