STRUCTURAL BIOLOGY OF VIRAL AND BACTERIAL VIRULENCE FACTORS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们有几个项目研究与病毒和细菌致病机制有关的关键酶和其他毒力因子的结构和功能。 我们最近的诺瓦克病毒聚合酶复制复合物的结构测定揭示了几个新的功能，需要进一步的结构工作，以更精确地确定在这个关键的抗病毒药物开发目标的催化和抑制的机制。 我们最近对艰难梭菌毒素结合碳水化合物受体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。 需要在该系统中进行进一步的结构工作，以确定碳水化合物识别的特异性和亲合力的基础要素，这将为开发新的C.艰难感染。 关于对结核分枝杆菌细胞壁碳水化合物生物合成重要的酶的较新项目已经产生了可能需要MAD或SAD定相来协助结构确定的晶体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. 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. 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.