Date of Award

5-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

Nina Goodey

Committee Member

David Konas

Committee Member

Jaclyn Catalano

Abstract

Mycobacterium tuberculosis is a bacterium that affects the lungs and causes tuberculosis, infecting over 10 million people worldwide each year. Owing to the organism’s evolving drug resistance, existing antibiotics no longer combat the disease. The need to discover new drug targets has never been greater. Previous findings suggest that the protein IGPS (indole-3-glycerol phosphate synthase) in M. tuberculosis (MtIGPS) may be a target in the treatment of the disease. MtIGPS catalyzes the fourth step in the tryptophan biosynthetic process. The ability to create their own tryptophan is a major advantage that many bacteria have. The role of E168, in the active site of MtIGPS was investigated. Wildtype and E168D MtIGPS proteins were then purified and KM values were determined to be 6.9 ± 1.4 μM and 26 ± 3 μM, respectively. After this, Wildtype and E168D kcat values were determined to be 0.022 ± 0.002 s-1 and 0.011 ± 0.001 s-1, respectively. An enhanced understanding of ligand binding and catalysis in the MtIGPS active site will aid in the design of MtIGPS inhibitors.

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