par Wohlkonig, Alexandre ;Remaut, Han;Moune, Martin;Tanina, Abdalkarim;Meyer, Franck ;Desroses, Matthieu;Steyaert, Jan;Willand, Nicolas;Baulard, Alain;Wintjens, René
Référence Biochemical and biophysical research communications, 487, 2, page (403-408)
Publication Publié, 2017-05
Référence Biochemical and biophysical research communications, 487, 2, page (403-408)
Publication Publié, 2017-05
Article révisé par les pairs
Résumé : | Inhibition of transcriptional regulators of bacterial pathogens with the aim of reprogramming their metabolism to modify their antibiotic susceptibility constitutes a promising therapeutic strategy. One example is the bio-activation of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by inhibiting the transcriptional repressor EthR. Recently, we discovered that inhibition of a second transcriptional repressor, EthR2, leads to the awakening of a new ethionamide bio-activation pathway. The x-ray structure of EthR2 was solved at 2.3 Å resolution in complex with a compound called SMARt-420 (Small Molecule Aborting Resistance). Detailed comparison and structural analysis revealed interesting insights for the upcoming structure-based design of EthR2 inhibitors as an alternative to revert ethionamide resistance in Mycobacterium tuberculosis. |