STRUCTURAL BIOLOGY OF VIRAL AND BACTERIAL VIRULENCE FACTORS

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。 我们有几个项目，研究与病毒和细菌致病相关的关键酶和其他毒力因子的结构和功能。我们最近对诺沃克病毒聚合酶复制复合体的结构测定揭示了几个新的特征，需要进一步的结构工作来更准确地确定这一抗病毒药物开发的关键靶点的催化和抑制机制。我们最近对艰难梭菌毒素与碳水化合物受体结合的受体结合片段的结构测定首次显示了受体识别的结构基础。在这个系统中还需要进一步的结构工作，以确定碳水化合物识别的特异性和亲和力的潜在要素，这将为开发艰难梭菌感染的新治疗方法提供基础。对结核分枝杆菌细胞壁碳水化合物的生物合成至关重要的酶的新项目已经产生了可能需要MAD或SAD阶段来辅助结构确定的晶体。

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. We have several projects investigating the structure and function of key enzymes and other virulence factors involved with viral and bacterial pathogenesis. Our recent structure determination of Norwalk virus polymerase replication complexes reveal several novel features that demand further structural work to determine more precisely the mechanisms underlying catalysis and inhibition in this key target for antiviral drug development. Our recent structure determination of receptor-binding fragments from Clostridium difficile toxins bound to carbohydrate receptors showed for the first time the structural basis underlying receptor recognition. Further structural work is needed in this system to define the elements underlying the specificity and avidity of carbohydrate recognition that will provide the basis for developing novel treatments for C. difficile infections. Newer projects on enzymes important for the biosynthesis of cell wall carbohydrates in Mycobacterium tuberculosis have yielded crystals that may need MAD or SAD phasing to assist with structure determination.