Structure-guided identification and characterization of potent inhibitors targeting PhoP and MtrA to combat mycobacteria.

ABSTRACT: Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified eff

SUBMITTER: Su HL 

PROVIDER: S-EPMC11016868 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature