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

High-field NMR spectroscopy has been used to study the complex formed by the tetrasaccharide sialyl Lewis X and its receptor, E-selectin. Tr ansferred 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 betwe en Overhauser spectra for free and bound sialyl Lewis X highlight a co nformational change upon binding. This can be pinpointed to a change i n the torsion angle of the glycosidic link between the sialyl and gala ctosyl residues and used to select a likely ''bound'' conformation fro m four low-energy species. Docking the bound form of sialyl Lewis X on to a model of the lectin domain of E-selectin suggests that the confor mational change upon binding results primarily from steric interaction s.