Conformational Selection in Glycomimetics: Human Galectin-1 Only Recognizes syn-Psi-Type Conformations of beta-1,3-Linked Lactose and Its C-Glycosyl Derivative
Résumé
The human lectin galectin-1 (hGal-1) translates sugar signals, that is, beta-galactosides, into effects on the level of cells, for example, growth regulation, and has become a model for studying binding of biopharmaceutically relevant derivatives. Bound-state conformations of Gal beta-C-(1 -> 3)-Glc beta-OMe (1) and its beta Gal-(1 -> 3)-beta Glc-OMe disaccharide parent compound were studied by using NMR spectroscopy (transferred (TR)-NOESY data), assisted by docking experiments and molecular dynamics (MD) simulations. The molecular recognition process involves a conformational selection event. Although free C-glycoside access four distinct conformers in solution, hGal-1 recognizes shape of a local minimum of compound 1, the syn-Phi/syn-Psi conformer, not the structure at global minimum. MD simulations were run to explain, in structural terms, the observed geometry of the complex