MYCOBACTERIAL TUBERCULOSIS PROTEASOME

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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. Mycobacterium tuberculosis (Mtb) persistently infects about two billion people. The identification of pathways used by the microbe to resist eleimination by the host immune response may suggest new targets for prevention or treatment of tuberculosis. Several mutants of Mtb with the insertions in proteasome-associated genes have been identified by Darwin, etc. (2003) that are required to resist nitric oxide and other reactive nitrogen intermediates (RNI). To understand and interpret how mycobacterial proteasome severs as a defense agaist oxidative or nitrosative stress, the crystal structures of Mtb proteins with the inhibitors are deserved to be determinated. Although we have obtained cryo-EM images of Mtb proteasome in 20 angstroms, we need the x-ray protein structures at the residue level (at least 3 angstroms) for the details. We have already crystallized the Mtb proteins and we are expecting to use synchrotron beamlines to collect the diffraction data.