IDENTIFICATION OF THE STRUCTURE OF A TB VIRULENCE FACTOR

这个子项目是许多研究子项目中的一个 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。 结核病的病原体是结核分枝杆菌（Mtb）。 这种致病细菌感染了世界三分之一的人口，每年造成200多万人死亡，超过任何其他传染病。结核病结构基因组学联盟旨在确定介导感染和持久性的蛋白质的晶体结构。 我们的研究小组已经结晶了一种完整膜蛋白的细胞外结构域，该蛋白已被证明是结核病的毒力因子。 晶体具有高度衍射性（1.2 <$分辨率）。 我们有初步的生物化学证据的身份的配体为这个胞外结构域，并将尝试共结晶和浸泡实验，以确定结合机制。 这种配体及其结合机制的鉴定有望为结核病毒力提供新的见解，并可能为减轻结核病感染提供新的靶点。

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. The causative agent of tuberculosis is Mycobacterium tuberculosis (Mtb). This pathogenic bacterium infects one third of the world's population and kills over two million people annually, more than any other infectious disease. The TB Structural Genomics Consortium is aimed at determining the crystal structures of the proteins that mediate infection and persistence. Our group has crystallized the extra-cellular domain of an integral membrane protein which has been shown to be a virulence factor for TB. The crystals are highly diffracting (1.2 ¿ resolution). We have preliminary biochemical evidence as to the identity of the ligand for this extracellular domain and will be attempting both co-crystallisation and soaking experiments to determine the binding mechanism. Identification of this ligand and its binding mechanism is expected to give new insights into TB virulence and may provide a new target for attenuating TB infection.