Investigating the KshB V246S Mutation in the KshAB Protein Complex Found in Mycobacterium Tuberculosis

Author Information

Malika Cruickshank, Bridgewater State University

Abstract/Description

This research centered on studying the interactions between the KshA and KshB subunits of the 3-ketosteroid-9α hydroxylase (KshAB) protein complex found in Mycobacterium tuberculosis (M. tuberculosis). Interactions between the two protein subunits were computationally explored using the protein docking program ClusPro and a location in the KshB subunit at Val 246 was found to be in proximity with nearby amino acids in the KshA subunit. This was determined to be a possible location for docking the protein complex. Val 246 of KshB was mutated into a serine residue to explore changes in the electron transfer pathway upon disruption of this interaction. The V246S KshB protein was successfully overexpressed in E. coli cells and purified by Ni-NTA chromatography. Initial enzyme kinetic analysis of the mutated protein complex is now underway. Future research will allow a deeper investigation into whether this mutation will inhibit the flow of electrons from the KshB subunit to the KshA subunit. The longterm goal is to design small molecules that can inhibit the electron flow in the native protein complex that would serve as antibiotics against M. tuberculosis infection. unit. The long-term goal is to design small molecules that can inhibit the electron flow in the native protein complex that would serve as antibiotics against M. tuberculosis infection.

Note on the Author

Malika Cruickshank graduated in 2023 with a degree in Chemistry, concentration in Professional Chemistry, and two minors, in Mathematics and Psychology. Her research took place over the course of three years under the mentorship of Dr. Sarah R. Soltau (Chemical Sciences) and with the support of multiple grants, including the Adrian Tinsley Program summer research grant and the SEISMIC grant through the National Science Foundation. Malika presented variations of this research at the 2022 National Conference on Undergraduate Research (NCUR) and at BSU’s Adrian Tinsley Program (ATP) Symposium. She plans to pursue an MD/DO to practice pediatric surgery.

Recommended Citation

Cruickshank, Malika (2023). Investigating the KshB V246S Mutation in the KshAB Protein Complex Found in Mycobacterium Tuberculosis. Undergraduate Review, 17, p. 9-22.
Available at: https://vc.bridgew.edu/undergrad_rev/vol17/iss1/5

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