Bovine heart galectin-1 selects a unique (Syn) conformation of C-lactose, a flexible lactose analogue

The C-glycoside analogue of lactose harbors a pronounced flexibility in wat er with three conformers in equilibrium. The bound conformation of C-lactos e to bovine heart galectin-1 in solution has been determined by NMR spectro scopy. It is demonstrated that the lectin selects the syn conformation of t he structural analogue of natural lactose and not the global minimum, anti conformation. The bound conformer resembles those found in the crystal stru ctures of complexes of galectin-1/N-acetyllactosamine-containing oligosacch arides and in solution for an avian galectin. Docking of the analogue withi n the galectin's binding site furnishes explanations, in structural terms, for the exclusive recognition of the syn conformer.