id="title" class="nomar"Structures of Mtb Proteins Conferring Susceptibility to Known Mtb Inhibitors
This biological project consists of investigators from Texas A&M University, Los Alamos National Laboratory, and the Harvard School of Public Health. It is partnered with the PSI High-Throughtput Structure Determination center MCSG.
- Texas A&M University
- Los Alamos National Laboratory
- Harvard School of Public Health
The overall goal of our center is to identify potential drug targets and companion inhibitors that inhibit growth of Mycobacterium tuberculosis, Pseudomonas aeruginosa and Staphylococcus aureus, in order to develop a foundation for antimicrobial drug discovery against gram positive and gram negative bacteria. Proteins that are targets of inhibitors (e.g. known drugs, or compounds from high-throughput screening) will be identified by genetic and complementary biochemical approaches. Structures will be determined, in collaboration with the Midwest Structural Genomic Consortium, of either the proteins that are targets of inhibitors or close homologs of these proteins. The structural information and inhibitor identities will be used along with annotations of related proteins to suggest molecular functions for each target protein. Assays for these molecular functions will be carried out to confirm both function and inhibition. Once targets are identified, their inhibitors will additionally be analyzed for their activity against other pathogenic bacteria and eukaryotic cell lines. The targets will then be prioritized for struture determination based on their novelty, the spectrum of activity of the companion growth inhibitor and the potency of the inhibitor. These structures, and biochemical information about the proteins will provide a rich resource of lead compounds and biochemistry for drug discovery, a foundation for understanding biology, and a path forward in the effort to improve human health by curing infectious disease.