THE CONFORMATION OF THE SIALYL-LEWIS-X LIGAND CHANGES UPON BINDING TO E-SELECTIN

High-field NMR spectroscopy has been used to study the complex formed by the tetrasaccharide sialyl Lewis X and its receptor, E-selectin. Transferred NOEs demonstrate a specific interaction between the protein and ligand and enable measurement of the dissociation constant for the complex to be between approximately 1.1 and 2.0 mM. Differences between Overhauser spectra for free and bound sialyl Lewis X highlight a conformational change upon binding. This can be pinpointed to a change in the torsion angle of the glycosidic link between the sialyl and galactosyl residues and used to select a likely ''bound'' conformation from four low-energy species. Docking the bound form of sialyl Lewis X onto a model of the lectin domain of E-selectin suggests that the conformational change upon binding results primarily from steric interactions.