5n7o

Publication Abstract from PubMed

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 A 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.

Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the Mycobacterium tuberculosis repressor EthR2.,Wohlkonig A, Remaut H, Moune M, Tanina A, Meyer F, Desroses M, Steyaert J, Willand N, Baulard AR, Wintjens R Biochem Biophys Res Commun. 2017 Apr 14. pii: S0006-291X(17)30750-7. doi:, 10.1016/j.bbrc.2017.04.074. PMID:28416386^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.