Concanavalin A distorts the beta-GlcNAc-(1-->2)-Man linkage of beta- GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man- (1-- >6)]-Man upon binding

Carbohydrate recognition by proteins is a key event in many biologicalprocesses. Concanavalin A is known to specifically recognize thepentasaccharide core (beta-GlcNAc-(1-->2)-alpha- Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man-(1-->6)]-Man) of N-linked oligosaccharideswith a Ka of 1.41 x 10(6 )M-1. We have determined the structure ofconcanavalin A bound to beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man- (1-->6)]-Man to 2.7A. In six of eightsubunits there is clear density for all five sugar residues and a wellordered binding site. The pentasaccharide adopts the same conformation inall eight subunits. The binding site is a continuous extended cleft on thesurface of the protein. Van der Waals interactions and hydrogen bondsanchor the carbohydrate to the protein. Both GlcNAc residues contact theprotein. The GlcNAc on the 1-->6 arm of the pentasaccharide makesparticularly extensive contacts and including two hydrogen bonds. Thebinding site of the 1-->3 arm GlcNAc is much less extensive.Oligosaccharide recognition by Con A occurs through specific proteincarbohydrate interactions and does not require recruitment of adventitiouswater molecules. The beta-GlcNAc-(1-->2)-Man glycosidic linkage PSItorsion angle on the 1-->6 arm is rotated by over 50 degrees from thatobserved in solution. This rotation is coupled to disruption ofinteractions at the monosaccharide site. We suggest destabilization of themonosaccharide site and the conformational strain reduces the free energyliberated by additional interactions at the 1-->6 arm GlcNAc site.