Physical Sciences and Mathematics Commons^™

Novel Inhibitors To Mmpl3 Transporter Of Mycobacterium Tuberculosis By Structure-Based High-Throughput Virtual Screening And Molecular Dynamics Simulations, Hetanshi Choksi, Justin Carbone, Nicholas J. Paradis, Lucas Bennett, Candice Bui-Linh, Chun Wu

Faculty Scholarship for the College of Science & Mathematics

Tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis (Mtb) utilizes mycolic acids for building the mycobacterial cell wall, which is critical in providing defense against external factors and resisting antibiotic action. MmpL3 is a secondary resistance nodulation division transporter that facilitates the coupled transport of mycolic acid precursor into the periplasm using the proton motive force, thus making it an attractive drug target for TB infection. In 2019, X-ray crystal structures of MmpL3 from M. smegmatis were solved with a promising inhibitor SQ109, which showed promise against drug-resistant TB in Phase II clinical trials. Still, there is a pressing need to discover more …