1w8h: Difference between revisions

One of the mechanisms contributing to the protection by breast-feeding of, the newborn against enteric diseases is related to the ability of human, milk oligosaccharides to prevent the 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 the present 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-fucosyl-lactose (Lewis x glucose analogue) bind to the lectin with, dissociation constants of 2.2x10(-7) M and 3.6x10(-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.

1W8H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with CA, SO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W8H OCA].  

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