6YO3

LecA from Pseudomonas aeruginosa in complex with a catechol CAS no. 67984-81-0

Summary for 6YO3

• Entry DOI: 10.2210/pdb6yo3/pdb
• Descriptor: PA-I galactophilic lectin, CALCIUM ION, 2,3-bis(oxidanyl)benzenecarbonitrile, ... (8 entities in total)
• Functional Keywords: non-carbohydrate glycomimetics, pains, lectin, catechols, sugar binding protein
• Biological source: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• Total number of polymer chains: 4
• Total formula weight: 52261.97

Authors

Kuhaudomlarp, S.,Imberty, A.,Titz, A. (deposition date: 2020-04-14, release date: 2020-12-30, Last modification date: 2024-01-24)

Primary citation

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., 60:8104-8114, 2021

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

Experimental method

X-RAY DIFFRACTION (1.84 Å)