title: NMR investigations of protein-carbohydrate interactions: insights into the topology of the bound conformation of a lactose isomer and beta-galactosyl xyloses to mistletoe lectin and galectin-1.
abstract: A hallmark of oligosaccharides is their often limited spatial flexibility, allowing them to access a distinct set of conformers in solution. Viewing each individual or even the complete ensemble of conformations as potential binding partner(s) for lectins in protein-carbohydrate interactions, it is pertinent to address the question on the characteristics of bound state conformation(s) in solution. Also, it is possible that entering the lectin's binding site distorts the low-energy topology of a glycosidic linkage. As a step to delineate the strategy of ligand selection for galactosides, a common physiological docking point, we have performed a NMR study on two non-homologous lectins showing identical monosaccharide specificity. Thus, the conformation of lactose analogues bound to bovine heart galectin-1 and to mistletoe lectin in solution has been determined by transferred nuclear Overhauser effect measurements. It is demonstrated that the lectins select the syn conformation of lactose and various structural analogues (Galbeta(1-->4)Xyl, Galbeta(1-->3)Xyl, Galbeta(1-->2)Xyl, and Galbeta(1-->3)Glc) from the ensemble of presented conformations. No evidence for conformational distortion was obtained. Docking of the analogues to the modeled binding sites furnishes explanations, in structural terms, for exclusive recognition of the syn conformer despite the non-homologous design of the binding sites.
authors.affiliation: Janssen-Cilag, Centro de Investigación Básica, Toledo, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Alonso-Plaza
authors.forename: M A
authors.initials: MA
authors.lastname: Canales
authors.forename: M
authors.initials: M
authors.lastname: Jiménez
authors.forename: J L
authors.initials: JL
authors.lastname: Roldán
authors.forename: A
authors.initials: A
authors.lastname: García-Herrero
authors.forename: L
authors.initials: L
authors.lastname: Iturrino
authors.forename: J L
authors.initials: JL
authors.lastname: Asensio
authors.forename: F J
authors.initials: FJ
authors.lastname: Cañada
authors.forename: A
authors.initials: A
authors.lastname: Romero
authors.forename: H C
authors.initials: HC
authors.lastname: Siebert
authors.forename: S
authors.initials: S
authors.lastname: André
authors.forename: D
authors.initials: D
authors.lastname: Solís
authors.forename: H J
authors.initials: HJ
authors.lastname: Gabius
authors.forename: J
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D001665:Binding Sites; D002240:Carbohydrate Sequence; D017666:Deuterium Oxide; D015195:Drug Design; D037483:Galectin 1; D006388:Hemagglutinins / Q000737:chemistry*; D041743:Herb-Drug Interactions; D007785:Lactose / Q000031:analogs & derivatives / Q000737:chemistry*; D037102:Lectins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D014784:Mistletoe; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012996:Solutions; D013499:Surface Properties; D014118:Toxins, Biological / Q000737:chemistry; D014994:Xylose / Q000737:chemistry*
chemical_list: D037483:Galectin 1; D006388:Hemagglutinins; D037102:Lectins; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012996:Solutions; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D014994:Xylose; D007785:Lactose; D017666:Deuterium Oxide