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

Biochem J. 2005 Jul 15;389(Pt 2):325-32. doi: 10.1042/BJ20050079.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / metabolism*
  • Binding Sites
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Crystallography
  • Humans
  • Lectins / metabolism*
  • Milk, Human / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Oligosaccharides / metabolism*
  • Protein Binding
  • Protein Conformation
  • Pseudomonas aeruginosa / chemistry*
  • Pseudomonas aeruginosa / metabolism
  • Substrate Specificity
  • Thermodynamics

Substances

  • Adhesins, Bacterial
  • Lectins
  • Oligosaccharides
  • adhesin, Pseudomonas