9QOT

APH(2'')-IVa with an inhibitor

これはPDB形式変換不可エントリーです。

9QOT の概要

• エントリーDOI: 10.2210/pdb9qot/pdb
• 関連するPDBエントリー: 9QOR
• 分子名称: APH(2'')-Id, 5-chloranyl-4-(1~{H}-1,2,3-triazol-4-yl)-1~{H}-pyrrolo[2,3-b]pyridine, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, enzyme, antibiotic
• 由来する生物種: Enterococcus casseliflavus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76414.13

構造登録者

Guichou, J.F.,Gelin, M.,Tomaszczyk, M.,Kowalewski, J.,Lionne, C. (登録日: 2025-03-26, 公開日: 2026-02-11)

主引用文献

Buffa, V.,Kowalewski, J.,Qi, G.,Deutscher, R.,Cica, M.,Richardoz, M.,Tomaszczyk, M.,Kramer, A.,Knapp, S.,Dunyach-Remy, C.,Rox, K.,Guichou, J.F.,Lionne, C.,Hausch, F.
Targeting bacterial kinases as a strategy to counteract antibiotic resistance.
Commun Chem, 8:390-390, 2025

PubMed Abstract: Antibiotic resistance is rapidly emerging as one of the most critical health threats, with resistant microorganisms progressively diminishing the effectiveness of established antibiotics. As a result, the development of therapeutic approaches that effectively target resistant pathogens is of utmost importance. In this study, we developed inhibitors for APH(2")-IVa, a bacterial kinase conveying resistance to aminoglycoside antibiotics. Starting from a hit of a fragment-based screening, we explored the inhibitory motif by structure-based design, ultimately leading to a series of triazole analogues. Advanced analogues displayed promising ADME properties, emerging selectivity vs a panel of human kinases, permeability in both Gram-positive and Gram-negative bacteria, and a moderate antibiotic efficacy for clinical strains of P. aeruginosa. Taken together, our results suggest inhibition of bacterial kinases could be a promising option to reinstall the efficacy of aminoglycoside antibiotics.

PubMed: 41345223
DOI: 10.1038/s42004-025-01794-7

実験手法

X-RAY DIFFRACTION (2.3 Å)