5MAY

STRUCTURE OF THE LECB LECTIN FROM PSEUDOMONAS AERUGINOSA STRAIN PA14 IN COMPLEX WITH 2-Thiophenesulfonamide-N-(beta-L-fucopyranosyl methyl)

5MAY の概要

• エントリーDOI: 10.2210/pdb5may/pdb
• 関連するPDBエントリー: 5a6q
• 分子名称: Fucose-binding lectin PA-IIL, CALCIUM ION, beta-L-fucopyranose, ... (5 entities in total)
• 機能のキーワード: sugar binding protein, lectin, lecb, pseudomonas aeruginosa pa14, glycoinhibitors
• 由来する生物種: Pseudomonas aeruginosa (strain UCBPP-PA14)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 48393.07

構造登録者

Sommer, R.,Imberty, A.,Titz, A.,Varrot, A. (登録日: 2016-11-07, 公開日: 2017-12-20, 最終更新日: 2024-01-17)

主引用文献

Sommer, R.,Wagner, S.,Rox, K.,Varrot, A.,Hauck, D.,Wamhoff, E.C.,Schreiber, J.,Ryckmans, T.,Brunner, T.,Rademacher, C.,Hartmann, R.W.,Bronstrup, M.,Imberty, A.,Titz, A.
Glycomimetic, Orally Bioavailable LecB Inhibitors Block Biofilm Formation of Pseudomonas aeruginosa.
J. Am. Chem. Soc., 140:2537-2545, 2018

PubMed Abstract: The opportunistic Gram-negative bacterium Pseudomonas aeruginosa is a leading pathogen for infections of immuno-compromised patients and those suffering from cystic fibrosis. Its ability to switch from planktonic life to aggregates, forming the so-called biofilms, is a front-line mechanism of antimicrobial resistance. The bacterial carbohydrate-binding protein LecB is an integral component and necessary for biofilm formation. Here, we report a new class of drug-like low molecular weight inhibitors of the lectin LecB with nanomolar affinities and excellent receptor binding kinetics and thermodynamics. This class of glycomimetic inhibitors efficiently blocked biofilm formation of P. aeruginosa in vitro while the natural monovalent carbohydrate ligands failed. Furthermore, excellent selectivity and pharmacokinetic properties were achieved. Notably, two compounds showed good oral bioavailability, and high compound concentrations in plasma and urine were achieved in vivo.

PubMed: 29272578
DOI: 10.1021/jacs.7b11133

実験手法

X-RAY DIFFRACTION (1.65 Å)