Progress on Evaluating Inhibition of Indole-3-Glycerol Phosphate Synthase from M. tuberculosis by rCdRP and rCdRP Analogs
Presentation Type
Poster
Faculty Advisor
David Konas
Access Type
Event
Start Date
26-4-2024 12:45 PM
End Date
26-4-2024 1:44 PM
Description
Indole-3-glycerol phosphate synthase from M. tuberculosis (MtIGPS) catalyzes the indole-forming reaction in the multi-step bacterial tryptophan biosynthetic pathway. This pathway appears to be necessary for bacterial growth and it could represent a target for potential new anti-infective agents in the future. In order to realize this possibility, more detailed information about MtIGPS enzyme-substrate interactions and its catalytic mechanism would be valuable. One goal of this work is to prepare and purify the reduced substrate analog rCdRP, which is not turned over to product, and determine its IC50 value. The second goal is to prepare additional rCdRP analogs with altered functional groups on the aromatic ring and determine their IC50 values. This will allow us to assess the importance of these groups for binding to the enzyme active site. Our current estimated/average IC50 value for rCdRP is 21µM and for the altered compounds we expect a higher IC50 value. In this presentation, current progress will be presented and discussed.
Progress on Evaluating Inhibition of Indole-3-Glycerol Phosphate Synthase from M. tuberculosis by rCdRP and rCdRP Analogs
Indole-3-glycerol phosphate synthase from M. tuberculosis (MtIGPS) catalyzes the indole-forming reaction in the multi-step bacterial tryptophan biosynthetic pathway. This pathway appears to be necessary for bacterial growth and it could represent a target for potential new anti-infective agents in the future. In order to realize this possibility, more detailed information about MtIGPS enzyme-substrate interactions and its catalytic mechanism would be valuable. One goal of this work is to prepare and purify the reduced substrate analog rCdRP, which is not turned over to product, and determine its IC50 value. The second goal is to prepare additional rCdRP analogs with altered functional groups on the aromatic ring and determine their IC50 values. This will allow us to assess the importance of these groups for binding to the enzyme active site. Our current estimated/average IC50 value for rCdRP is 21µM and for the altered compounds we expect a higher IC50 value. In this presentation, current progress will be presented and discussed.