Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin PA-IIL of Pseudomonas aeruginosa.
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.
Perret
Stéphanie
S
Centre de Recherches sur les Macromolécules Végétales, CNRS, Université Joseph Fourier, BP53, 38041 Grenoble Cedex 09, France.
Sabin
Charles
C
Dumon
Claire
C
Pokorná
Martina
M
Gautier
Catherine
C
Galanina
Oxana
O
Ilia
Shahov
S
Bovin
Nicolai
N
Nicaise
Magali
M
Desmadril
Michel
M
Gilboa-Garber
Nechama
N
Wimmerová
Michaela
M
Mitchell
Edward P
EP
Imberty
Anne
A
D018829:Adhesins, Bacterial / Q000378:metabolism*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003461:Crystallography; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics
D018829:Adhesins, Bacterial; D037102:Lectins; D009844:Oligosaccharides; C038692:adhesin, Pseudomonas