Study of molecular mechanisms of a Mycobacterium tuberculosis repressor by CryoEM analysis

During our screens for finding new small molecules with anti-TB capacity, we identified a gene controlling the expression of a putative efflux pump in Mycobacterium tuberculosis, the causative agent of TB. Gene names are voluntarily omitted, for confidentiality reason. The gene product is a repressor protein belonging to a well-known family of transcriptional factors whose mechanism of action has never been explicitly demonstrated. Furthermore, controlling the action of this repressor may have therapeutic potential when combined with the use of some commercial anti-TB drugs. Hence, to modulate activity of the repressor, we first must gain insight into how this protein works. This question will be addressed in the present project by using cryo-EM thorough analysis in combination with the functional data already acquired.