7Z63

Structure of the LecA lectin from Pseudomonas aeruginosa in complex with a biaryl-thiogalactoside

This is a non-PDB format compatible entry.

Summary for 7Z63

• Entry DOI: 10.2210/pdb7z63/pdb
• Descriptor: PA-I galactophilic lectin, CALCIUM ION, [3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]sulfanyl-4-methoxy-phenyl]-(3,4,5-trimethoxyphenyl)methanone, ... (5 entities in total)
• Functional Keywords: lectin, antiadhesive, thiogalactoside, rna binding protein, sugar binding protein
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 4
• Total formula weight: 53289.04

Authors

Varrot, A. (deposition date: 2022-03-10, release date: 2023-01-18, Last modification date: 2024-01-31)

Primary citation

Bruneau, A.,Gillon, E.,Furiga, A.,Brachet, E.,Alami, M.,Roques, C.,Varrot, A.,Imberty, A.,Messaoudi, S.
Discovery of potent 1,1-diarylthiogalactoside glycomimetic inhibitors of Pseudomonas aeruginosa LecA with antibiofilm properties.
Eur.J.Med.Chem., 247:115025-115025, 2022

PubMed Abstract: In this work, β-thiogalactoside mimetics bearing 1,1-diarylmethylene or benzophenone aglycons have been prepared and assayed for their affinity towards LecA, a lectin and virulence factor from Pseudomonas aeruginosa involved in bacterial adhesion and biofilm formation. The hit compound presents higher efficiency than previously described monovalent inhibitors and the crystal structure confirmed the occurrence of additional contacts between the aglycone and the protein surface. The highest affinity (160 nM) was obtained for a divalent ligand containing two galactosides. The monovalent high affinity compound (K = 1 μM) obtained through structure-activity relationship (SAR) showed efficient antibiofilm activity with no associated bactericidal activity.

PubMed: 36549118
DOI: 10.1016/j.ejmech.2022.115025

Experimental method

X-RAY DIFFRACTION (1.75 Å)