Pseudomonas aeruginosa galactose- and fucose-binding (PA-IL and PA-IIL) lectins contribute to the virulence of this pathogenic bacterium, which is a major cause of morbidity and mortality in cystic fibrosis patients. The crystal structure of PA-IIL complexed with fucose has been solved at 1.3 A and further refined at 1 Ĺ resolution. Additional experiments have been performed in order to understand the molecular basis of both specificity and affinity of PA-IIL for monosaccharides. Crystals have been obtained for the complex between PA-ILL and b-Me-D-arabinopyranoside and the structure has been solved at 1.8 A resolution. PA-IIL exhibits unusually high specificity to fucose, which can be related to the presence of two calcium ions in the site. Isothermal titration microcalorimetry (ITC) experiments were performed in order to characterize the thermodynamic parameters of the interaction since this method has been proven to be well adapted to the study of protein/carbohydrate interactions. Several monosaccharides differing only by the group at C5 (L-fucose, L-galactose and D-arabinose) were tested, as well as their methyl-glycosides. Calculations of charges distribution were performed using quantum chemistry in order to rationalize the role of calcium ions in the affinity.