9FQD

Pseudomonas aeruginosa Elastase in complex with a phosphonate based inhibitor (R-configured)

これはPDB形式変換不可エントリーです。

9FQD の概要

• エントリーDOI: 10.2210/pdb9fqd/pdb
• 分子名称: Elastase, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: virulence factor, inhibitor, complex, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33720.29

構造登録者

Klein, A.,Hirsch, A. (登録日: 2024-06-16, 公開日: 2025-06-25, 最終更新日: 2025-08-27)

主引用文献

Kiefer, A.F.,Schutz, C.,Englisch, C.N.,Kolling, D.,Speicher, S.,Kany, A.M.,Shafiei, R.,Wadood, N.A.,Aljohmani, A.,Wirschem, N.,Jumde, R.P.,Klein, A.,Sikandar, A.,Park, Y.M.,Krasteva-Christ, G.,Yildiz, D.,Abdelsamie, A.S.,Rox, K.,Kohnke, J.,Muller, R.,Bischoff, M.,Haupenthal, J.,Hirsch, A.K.H.
Dipeptidic Phosphonates: Potent Inhibitors of Pseudomonas aeruginosa Elastase B Showing Efficacy in a Murine Keratitis Model.
Adv Sci, 12:e2411807-e2411807, 2025

PubMed Abstract: The ubiquitous opportunistic pathogen Pseudomonas aeruginosa is responsible for severe infections and notoriously known for acquiring antimicrobial resistance. Inhibiting the bacterium's extracellular elastase, LasB - a zinc-dependent protease - presents a promising strategy to mitigate its virulence. Within this medicinal chemistry-driven hit-to-lead optimization campaign, a new series of highly potent dipeptidic phosphonates is designed and synthesized following a structure-based drug-discovery approach. In vitro and in vivo evaluation reveal beneficial pharmacokinetic profiles, excellent selectivity over human off-targets and good tolerability in murine toxicity studies. Ultimately, the scaffold presented herein demonstrates promising in vivo efficacy in a murine Pseudomonas aeruginosa keratitis model in combination with the antibiotic meropenem.

PubMed: 39973061
DOI: 10.1002/advs.202411807

実験手法

X-RAY DIFFRACTION (1.7 Å)