4A6S

Structure of the PAIL lectin from Pseudomonas aeruginosa in complex with 2-Naphtyl-1-thio-beta-D-galactopyranoside

Summary for 4A6S

• Entry DOI: 10.2210/pdb4a6s/pdb
• Related: 1L7L 1OKO 1UOJ 2VXJ 2WYF 3ZYB 3ZYF 3ZYH
• Descriptor: PA-I GALACTOPHILIC LECTIN, CALCIUM ION, naphthalen-2-yl 1-thio-beta-D-galactopyranoside, ... (4 entities in total)
• Functional Keywords: sugar-binding protein, glycomimetic, sugar binding protein
• Biological source: PSEUDOMONAS AERUGINOSA
• Cellular location: Cytoplasm: Q05097
• Total number of polymer chains: 4
• Total formula weight: 52530.36

Authors

Rodrigue, J.,Ganne, G.,Blanchard, B.,Saucier, C.,Giguere, D.,Chiao, T.S.,Varrot, A.,Imberty, A.,Roy, R. (deposition date: 2011-11-08, release date: 2012-10-17, Last modification date: 2023-12-20)

Primary citation

Rodrigue, J.,Ganne, G.,Blanchard, B.,Saucier, C.,Giguere, D.,Shiao, T.C.,Varrot, A.,Imberty, A.,Roy, R.
Aromatic Thioglycoside Inhibitors Against the Virulence Factor Leca from Pseudomonas Aeruginosa.
Org.Biomol.Chem., 11:6906-, 2013

PubMed Abstract: Three small families of hydrolytically stable thioaryl glycosides were prepared as inhibitors of the LecA (PA-IL) virulence factor corresponding to the carbohydrate binding lectin from the bacterial pathogen Pseudomonas aeruginosa. The monosaccharidic arylthio β-d-galactopyranosides served as a common template for the major series that was also substituted at the O-3 position. Arylthio disaccharides from lactose and from melibiose constituted the other two series members. In spite of the fact that the natural ligand for LecA is a glycolipid of the globotriaosylceramide having an α-d-galactopyranoside epitope, this study illustrated that the β-d-galactopyranoside configuration having a hydrophobic aglycon could override the requirement toward the anomeric configuration of the natural sugar. The enzyme linked lectin assay together with isothermal titration microcalorimetry established that naphthyl 1-thio-β-d-galactopyranoside () gave the best inhibition with an IC50 twenty-three times better than that of the reference methyl α-d-galactopyranoside. In addition it showed a KD of 6.3 μM which was ten times better than that of the reference compound. The X-ray crystal structure of LecA with was also obtained.

PubMed: 24057051
DOI: 10.1039/C3OB41422A

Experimental method

X-RAY DIFFRACTION (2.15 Å)