5N7O

EthR2 in complex with SMARt-420 compound

Summary for 5N7O

• Entry DOI: 10.2210/pdb5n7o/pdb
• Related: 5ICJ 5N1C 5N1I
• Descriptor: Probable transcriptional regulatory protein, 4,4,4-trifluoro-1-(3-phenyl-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl)butan-1-one (3 entities in total)
• Functional Keywords: repressor, complex, inhibitor, transcription
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 48925.82

Authors

Wohlkonig, A.,Wintjens, R. (deposition date: 2017-02-21, release date: 2017-04-26, Last modification date: 2024-01-17)

Primary citation

Wohlkonig, A.,Remaut, H.,Moune, M.,Tanina, A.,Meyer, F.,Desroses, M.,Steyaert, J.,Willand, N.,Baulard, A.R.,Wintjens, R.
Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the Mycobacterium tuberculosis repressor EthR2.
Biochem. Biophys. Res. Commun., 487:403-408, 2017

PubMed Abstract: 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.

PubMed: 28416386
DOI: 10.1016/j.bbrc.2017.04.074

Experimental method

X-RAY DIFFRACTION (2.3 Å)