1w8f
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| , resolution 1.05Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
PSEUDOMONAS AERUGINOSA LECTIN II (PA-IIL) COMPLEXED WITH LACTO-N-NEO-FUCOPENTAOSE V(LNPFV)
OverviewOverview
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.
About this StructureAbout this Structure
1W8F is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin PA-IIL of Pseudomonas aeruginosa., Perret S, Sabin C, Dumon C, Pokorna M, Gautier C, Galanina O, Ilia S, Bovin N, Nicaise M, Desmadril M, Gilboa-Garber N, Wimmerova M, Mitchell EP, Imberty A, Biochem J. 2005 Jul 15;389(Pt 2):325-32. PMID:15790314
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