title: NMR and MD investigations of human galectin-1/oligosaccharide complexes.
abstract: The specific recognition of carbohydrates by lectins plays a major role in many cellular processes. Galectin-1 belongs to a family of 15 structurally related beta-galactoside binding proteins that are able to control a variety of cellular events, including cell cycle regulation, adhesion, proliferation, and apoptosis. The three-dimensional structure of galectin-1 has been solved by x-ray crystallography in the free form and in complex with various carbohydrate ligands. In this work, we used a combination of two-dimensional NMR titration experiments and molecular-dynamics simulations with explicit solvent to study the mode of interaction between human galectin-1 and five galactose-containing ligands. Isothermal titration calorimetry measurements were performed to determine their affinities for galectin-1. The contribution of the different hexopyranose units in the protein-carbohydrate interaction was given particular consideration. Although the galactose moiety of each oligosaccharide is necessary for binding, it is not sufficient by itself. The nature of both the reducing sugar in the disaccharide and the interglycosidic linkage play essential roles in the binding to human galectin-1.
authors.affiliation: Unité Interactions et Modulateurs de Réponses, Institut de Microbiologie de la Méditerrannée, Centre National de la Recherche Scientifique, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Meynier
authors.forename: Mikael
authors.initials: M
authors.lastname: Feracci
authors.forename: Marion
authors.initials: M
authors.lastname: Espeli
authors.forename: Florence
authors.initials: F
authors.lastname: Chaspoul
authors.forename: Philippe
authors.initials: P
authors.lastname: Gallice
authors.forename: Claudine
authors.initials: C
authors.lastname: Schiff
authors.forename: Françoise
authors.initials: F
authors.lastname: Guerlesquin
authors.forename: Philippe
authors.initials: P
authors.lastname: Roche
mesh_terms: D002151:Calorimetry; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism; D005690:Galactose / Q000737:chemistry / Q000378:metabolism; D037483:Galectin 1 / Q000737:chemistry* / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D012984:Software; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D004187:Disaccharides; D037483:Galectin 1; D006027:Glycosides; D008024:Ligands; D009844:Oligosaccharides; D014867:Water; D005690:Galactose