Structural basis for the interaction between human milk oligosaccharides and a bacterial protein, Pseudomonas aeruginosa lectin PA-IIL,

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Authors

PERRET Stephanie SABIN Charles DUMON Claire POKORNÁ Martina GAUTIER Catherine GALANINA Oxana ILIA Shahov BOVIN Nicolai NICAISE Magali DESMADRIL Michel GILBOA-GARBER Nechama WIMMEROVÁ Michaela MITCHELL Edward P. IMBERTY Anne

Year of publication 2005
Type Article in Periodical
Magazine / Source Biochemical Journal
MU Faculty or unit

Faculty of Science

Citation
Field Biochemistry
Keywords lectin; Pseudomonas aeruginosa; cystic fibrosis; crystal structure; milk oligosaccharides
Description One of the mechanisms contributing to breast-feeding protection of the newborn against enteric diseases is related to the ability of human milk oligosaccharides to prevent attachment of pathogenic bacteria to the duodenual epithelium. Indeed, a variety of fucosylated oligosaccharides, specific to human milk, form part of the innate immune system. In this study, we demonstrate the specific blocking of PA-IIL, a fucose-binding lectin of the human pathogen Pseudomonas aeruginosa by milk oligosaccharides. Two fucosylated epitopes, Lewis a and 3-fucosyllactose (Lewis x glucose analogue) bind to the lectin with dissociation constants of 2.2 10-7 M and 3.6 10-7 M, respectively. Thermodynamic studies indicate that these interactions are dominated by enthalpy. The entropy contribution is slightly favourable when binding to fucose and to the highest affinity ligand, Lewis a. The high resolution X-ray structures of two complexes of PA-IIL with milk oligosaccharides allow the precise determination of the conformation of a trisaccharide and a pentasaccharide. The different types of interaction between the oligosaccharides and the protein involve not only hydrogen bonding, but also calcium- and water-bridged contacts, allowing a rationalization of the thermodynamic data. This study provides important structural information about compounds that could be of general application in new therapeutic strategies against bacterial infections.
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