Date of Award


Document Type


Degree Name

Master of Science (MS)


College of Science and Mathematics


Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

Nina M. Goodey

Committee Member

David Konas

Committee Member

Jaclyn Catalano


Tuberculosis (TB) is a disease that is caused by a bacteria called Mycobacterium tuberculosis and primarily attacks the lungs but can spread to other areas of the body as well. TB can develop resistance to drugs that may be used to cure the disease. Multidrug resistant TB is especially a growing issue as it does not respond to the two most powerful anti-TB drugs, isoniazid and rifampicin. For this reason, finding new ways to target TB are critically needed. One possible way to do this is to target the enzymes in the tryptophan biosynthetic pathway of M. tuberculosis. Studies have suggested that the enzyme indole-3-glycerol phosphate synthase (IGPS) in M. tuberculosis (MtIGPS) coded for by the trpC gene could be a target (Shen et al. 2009). The interactions between ligands and MtIGPS were thus investigated by introducing mutations to residues that had been proposed to play a role in catalysis or binding in the active. Specifically, E168 was mutated to glutamine, Q, K119 was mutated to arginine, R and K59 was also mutated to arginine, R. Predictions for these mutations were that K119 plays a role as a catalytic acid and that E168 plays a role as a possible catalytic base. We investigated the impact of these mutations on steady state kinetics and rate-pH profiles to obtain insights into the roles of these three residues in substrate binding and catalysis. These findings will facilitate the design of MtIGPS inhibitor candidates.

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