7UGW

M. tuberculosis DNA gyrase cleavage core bound to DNA and evybactin

これはPDB形式変換不可エントリーです。

7UGW の概要

• エントリーDOI: 10.2210/pdb7ugw/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002540
• 分子名称: DNA gyrase subunit A, DNA gyrase subunit B, DNA (46-MER), ... (5 entities in total)
• 機能のキーワード: topoisomerase, inhibitor, natural product, isomerase-antibiotic-dna complex, isomerase/antibiotic/dna
• 由来する生物種: Mycobacterium tuberculosis H37Rv; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 183784.17

構造登録者

Hauk, G.,Imai, Y.,Lewis, K.,Berger, J.M. (登録日: 2022-03-25, 公開日: 2022-08-17, 最終更新日: 2024-10-02)

主引用文献

Imai, Y.,Hauk, G.,Quigley, J.,Liang, L.,Son, S.,Ghiglieri, M.,Gates, M.F.,Morrissette, M.,Shahsavari, N.,Niles, S.,Baldisseri, D.,Honrao, C.,Ma, X.,Guo, J.J.,Berger, J.M.,Lewis, K.
Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis.
Nat.Chem.Biol., 18:1236-1244, 2022

PubMed Abstract: The antimicrobial resistance crisis requires the introduction of novel antibiotics. The use of conventional broad-spectrum compounds selects for resistance in off-target pathogens and harms the microbiome. This is especially true for Mycobacterium tuberculosis, where treatment requires a 6-month course of antibiotics. Here we show that a novel antimicrobial from Photorhabdus noenieputensis, which we named evybactin, is a potent and selective antibiotic acting against M. tuberculosis. Evybactin targets DNA gyrase and binds to a site overlapping with synthetic thiophene poisons. Given the conserved nature of DNA gyrase, the observed selectivity against M. tuberculosis is puzzling. We found that evybactin is smuggled into the cell by a promiscuous transporter of hydrophilic compounds, BacA. Evybactin is the first, but likely not the only, antimicrobial compound found to employ this unusual mechanism of selectivity.

PubMed: 35996001
DOI: 10.1038/s41589-022-01102-7

実験手法

X-RAY DIFFRACTION (3 Å)