5N1I

unliganded form of the Mycobacterium tuberculosis repressor EthR2

5N1I の概要

• エントリーDOI: 10.2210/pdb5n1i/pdb
• 関連するPDBエントリー: 5ICJ 5N1C
• 分子名称: Probable transcriptional regulatory protein (2 entities in total)
• 機能のキーワード: repressor, ethr, dna binding protein, tetr protein family.
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48245.14

構造登録者

Wintjens, R.,Wohlkonig, A. (登録日: 2017-02-06, 公開日: 2017-04-26, 最終更新日: 2025-01-29)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)