IDENTIFICATION OF THE STRUCTURE OF A TB VIRULENCE FACTOR

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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.