7z62
Structure of the LecA lectin from Pseudomonas aeruginosa in complex with a biaryl-thiogalactosideStructure of the LecA lectin from Pseudomonas aeruginosa in complex with a biaryl-thiogalactoside
Structural highlights
FunctionPA1L_PSEAE D-galactose specific lectin. Binds in decreasing order of affinity: melibiose, methyl-alpha-D-galactoside, D-galactose, methyl-beta-D-galactoside, N-acetyl-D-galactosamine. Similar to plant lectins in its selective (carbohydrate-specific) hemagglutinating activity. Publication Abstract from PubMedIn this work, beta-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(d) = 1 muM) obtained through structure-activity relationship (SAR) showed efficient antibiofilm activity with no associated bactericidal activity. Discovery of potent 1,1-diarylthiogalactoside glycomimetic inhibitors of Pseudomonas aeruginosa LecA with antibiofilm properties.,Bruneau A, Gillon E, Furiga A, Brachet E, Alami M, Roques C, Varrot A, Imberty A, Messaoudi S Eur J Med Chem. 2023 Feb 5;247:115025. doi: 10.1016/j.ejmech.2022.115025. Epub , 2022 Dec 15. PMID:36549118[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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