Critical Role of the Solvent Environment in Galectin-1 Binding to the Disaccharide Lactose

DI LELLA, SANTIAGO; MA, LU; DÍAZ RICCI, JUAN C.; RABINOVICH, GABRIEL A.; ASHER, SANFOR A.; ÁLVAREZ, MA. ROSA

BIOCHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington, USA; Año: 2009 vol. 48 p. 786 - 791

0006-2960

  Galectin-1, a member of a family of evolutionarily conserved glycan-binding proteins, binds specifically to poly-N-acetylactosamine-enriched glycoconjugates. Through interactions with specific glycoconjugates, this protein modulates the inflammatory response and contributes to tumor progression and immune cell homeostasis. The carbohydrate recognition domain includes the single protein tryptophan (Trp68). UV Resonance Raman spectroscopy and molecular dynamic simulation were used to examine the change in the environment of the Trp on ligand binding. The UV Raman spectra and the calculated water radial distribution function show that, while no large structural changes in the protein follows lactose binding, substantial solvent reorganization occurs. These new insights into the microscopic role of water molecules on Gal-1 binding to its specific carbohydrate ligands provides a better understanding the physicochemical properties of Gal-1-saccharide interactions, which will be useful for the design of synthetic inhibitors for therapeutic purposes.