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. Mycobacterium tuberculosis is a bacterial pathogen that causes tuberculosis, the worlds? most deadly infectious disease, which kills approximately two million people per year. Currently, one in three persons worldwide is infected with M. tuberculosis, and TB is also the current leading cause of death for AIDS patients. Recent data suggests that a previously uncharacterized heme acquisition system plays an important role in M. tuberculosis pathogenesis. My proposed research focuses on gaining a structural understanding of this novel mycobacterial heme acquisition system. Also, my proposal includes a novel pathway supposedly involved in fatty acid metabolism that has been shown to be essential for survival of Yersinia pestis in macrophages, and M. tuberculosis has a homologous pathway. Structural characterization of these proteins will allow us to functional characterize this important pathway. Time at the SSRL beam-line is paramount to the structural understanding of the proteins involved in these pathways with a goal of structure-based drug design for the development of therapeutics against tuberculosis (TB), which includes multi-drug resistant strains and latent TB infection.
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