9G3R

LecA from Pseudomonas aeruginosa in complex with a synthetic thiogalactoside

Summary for 9G3R

• Entry DOI: 10.2210/pdb9g3r/pdb
• Descriptor: PA-I galactophilic lectin, 1-thio-beta-D-galactopyranose-(1-1)-alpha-L-fucopyranose, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: lectin, cell adhesion, leca, pa-il, galactose-binding, sugar binding protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 8
• Total formula weight: 105029.89

Authors

Melicher, F.,Faltinek, L.,Wimmerova, M. (deposition date: 2024-07-12, release date: 2024-11-27, Last modification date: 2025-02-05)

Primary citation

Faltinek, L.,Melicher, F.,Kelemen, V.,Mezo, E.,Borbas, A.,Wimmerova, M.
Bispecific Thio-Linked Disaccharides as Inhibitors of Pseudomonas Aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy.
Chemistry, 31:e202403546-e202403546, 2025

PubMed Abstract: Pseudomonas aeruginosa is a prevalent opportunistic human pathogen, particularly associated with cystic fibrosis. Among its virulence factors are the LecA and LecB lectins. Both lectins play an important role in the adhesion to the host cells and display cytotoxic activity. In this study, we successfully synthesized hardly hydrolysable carbohydrate ligands targeting these pathogenic lectins, including two bispecific glycans. The interactions between LecA/LecB lectins and synthetic glycans were evaluated using hemagglutination (yeast agglutination) inhibition assays, comparing their efficacy with corresponding monosaccharides. Additionally, the binding affinities of bispecific glycans were assessed using isothermal titration calorimetry (ITC). Structural insight into the lectin-ligand interaction was obtained by determining the crystal structures of LecA/LecB lectins in complex with one of the bispecific ligands using X ray crystallography. This comprehensive investigation into the inhibitory potential of synthetic glycosides against P. aeruginosa lectins sheds light on their potential application in antimicrobial therapy.

PubMed: 39535852
DOI: 10.1002/chem.202403546

Experimental method

X-RAY DIFFRACTION (1.7 Å)