8AIY

STRUCTURE OF THE LECB LECTIN FROM PSEUDOMONAS AERUGINOSA STRAIN PAO1 IN COMPLEX WITH N-(beta-L-Fucopyranosyl)-biphenyl-3-carboxamide (4i)

これはPDB形式変換不可エントリーです。

8AIY の概要

• エントリーDOI: 10.2210/pdb8aiy/pdb
• 分子名称: Fucose-binding lectin PA-IIL, CALCIUM ION, N-(beta-L-Fucopyranosyl)-biphenyl-3-carboxamide, ... (5 entities in total)
• 機能のキーワード: p. aeruginosa lectin, lecb, inhibitor, sugar binding protein
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 48825.07

構造登録者

Meiers, J.,Mala, P.,Varrot, A.,Siebs, E.,Imberty, A.,Titz, A. (登録日: 2022-07-27, 公開日: 2022-11-02, 最終更新日: 2024-01-31)

主引用文献

Mala, P.,Siebs, E.,Meiers, J.,Rox, K.,Varrot, A.,Imberty, A.,Titz, A.
Discovery of N -beta-l-Fucosyl Amides as High-Affinity Ligands for the Pseudomonas aeruginosa Lectin LecB.
J.Med.Chem., 65:14180-14200, 2022

PubMed Abstract: The Gram-negative pathogen causes severe infections mainly in immunocompromised or cystic fibrosis patients and is able to resist antimicrobial treatments. The extracellular lectin LecB plays a key role in bacterial adhesion to the host and biofilm formation. For the inhibition of LecB, we designed and synthesized a set of fucosyl amides, sulfonamides, and thiourea derivatives. Then, we analyzed their binding to LecB in competitive and direct binding assays. We identified β-fucosyl amides as unprecedented high-affinity ligands in the two-digit nanomolar range. X-ray crystallography of one α- and one β-anomer of -fucosyl amides in complex with LecB revealed the interactions responsible for the high affinity of the β-anomer at atomic level. Further, the molecules showed good stability in murine and human blood plasma and hepatic metabolism, providing a basis for future development into antibacterial drugs.

PubMed: 36256875
DOI: 10.1021/acs.jmedchem.2c01373

実験手法

X-RAY DIFFRACTION (1.55 Å)