5N1I

unliganded form of the Mycobacterium tuberculosis repressor EthR2

Summary for 5N1I

• Entry DOI: 10.2210/pdb5n1i/pdb
• Related: 5ICJ 5N1C
• Descriptor: Probable transcriptional regulatory protein (2 entities in total)
• Functional Keywords: repressor, ethr, dna binding protein, tetr protein family.
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 2
• Total formula weight: 48245.14

Authors

Wintjens, R.,Wohlkonig, A. (deposition date: 2017-02-06, release date: 2017-04-26, Last modification date: 2025-01-29)

Primary citation

Blondiaux, N.,Moune, M.,Desroses, M.,Frita, R.,Flipo, M.,Mathys, V.,Soetaert, K.,Kiass, M.,Delorme, V.,Djaout, K.,Trebosc, V.,Kemmer, C.,Wintjens, R.,Wohlkonig, A.,Antoine, R.,Huot, L.,Hot, D.,Coscolla, M.,Feldmann, J.,Gagneux, S.,Locht, C.,Brodin, P.,Gitzinger, M.,Deprez, B.,Willand, N.,Baulard, A.R.
Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420.
Science, 355:1206-1211, 2017

PubMed Abstract: Antibiotic resistance is one of the biggest threats to human health globally. Alarmingly, multidrug-resistant and extensively drug-resistant have now spread worldwide. Some key antituberculosis antibiotics are prodrugs, for which resistance mechanisms are mainly driven by mutations in the bacterial enzymatic pathway required for their bioactivation. We have developed drug-like molecules that activate a cryptic alternative bioactivation pathway of ethionamide in , circumventing the classic activation pathway in which resistance mutations have now been observed. The first-of-its-kind molecule, named SMARt-420 (Small Molecule Aborting Resistance), not only fully reverses ethionamide-acquired resistance and clears ethionamide-resistant infection in mice, it also increases the basal sensitivity of bacteria to ethionamide.

PubMed: 28302858
DOI: 10.1126/science.aag1006

Experimental method

X-RAY DIFFRACTION (2.4 Å)