6YOH

LecA from Pseudomonas aeruginosa in complex with a catechol CAS no. 61445-50-9

6YOH の概要

• エントリーDOI: 10.2210/pdb6yoh/pdb
• 分子名称: PA-I galactophilic lectin, CALCIUM ION, [2,4-bis(oxidanyl)phenyl]-[3,4-bis(oxidanyl)phenyl]methanone, ... (4 entities in total)
• 機能のキーワード: non-carbohydrate glycomimetics, pains, lectin, catechols, 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: 51979.50

構造登録者

Kuhaudomlarp, S.,Imberty, A.,Titz, A.,Varrot, A. (登録日: 2020-04-14, 公開日: 2021-02-24, 最終更新日: 2024-01-24)

主引用文献

Kuhaudomlarp, S.,Siebs, E.,Shanina, E.,Topin, J.,Joachim, I.,da Silva Figueiredo Celestino Gomes, P.,Varrot, A.,Rognan, D.,Rademacher, C.,Imberty, A.,Titz, A.
Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-binding Lectins.
Angew.Chem.Int.Ed.Engl., 2020

PubMed Abstract: Because of the antimicrobial resistance crisis, lectins are considered novel drug targets. Pseudomonas aeruginosa utilizes LecA and LecB in the infection process. Inhibition of both lectins with carbohydrate-derived molecules can reduce biofilm formation to restore antimicrobial susceptibility. Here, we focused on non-carbohydrate inhibitors for LecA to explore new avenues for lectin inhibition. From a screening cascade we obtained one experimentally confirmed hit, a catechol, belonging to the well-known PAINS compounds. Rigorous analyses validated electron-deficient catechols as millimolar LecA inhibitors. The first co-crystal structure of a non-carbohydrate inhibitor in complex with a bacterial lectin clearly demonstrates the catechol mimicking the binding of natural glycosides with LecA. Importantly, catechol 3 is the first non-carbohydrate lectin ligand that binds bacterial and mammalian calcium(II)-binding lectins, giving rise to this fundamentally new class of glycomimetics.

PubMed: 33314528
DOI: 10.1002/anie.202013217

実験手法

X-RAY DIFFRACTION (1.84 Å)