title: Conformational selection of glycomimetics at enzyme catalytic sites: experimental demonstration of the binding of distinct high-energy distorted conformations of C-, S-, and O-glycosides by E. Coli beta-galactosidases.
abstract: We show that the conformational features of the molecular complexes of E. coli beta-galactosidase and O-glycosides may differ from those formed with closely related compounds in their chemical nature, such as C- and S-glycosyl analogues. In the particular case presented here, NMR and ab initio quantum mechanical results show that the 3D-shapes of the ligand/inhibitor within the enzyme binding site depend on the chemical nature of the compounds. In fact, they depend on the relative size of the stereoelectronic barriers for chair deformation or for rotation around Phi glycosidic linkage.
authors.affiliation: Department Bioorganic Chemistry, Instituto Quimica Organica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: García-Herrero
authors.forename: Esther
authors.initials: E
authors.lastname: Montero
authors.forename: Jose L
authors.initials: JL
authors.lastname: Muñoz
authors.forename: Juan F
authors.initials: JF
authors.lastname: Espinosa
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vián
authors.forename: Jose L
authors.initials: JL
authors.lastname: García
authors.forename: Juan L
authors.initials: JL
authors.lastname: Asensio
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.forename: Jesus
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D001665:Binding Sites; D002236:Carbohydrate Conformation; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry* / Q000378:metabolism; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011789:Quantum Theory; D013237:Stereoisomerism; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006027:Glycosides; D001616:beta-Galactosidase; D007785:Lactose