title: Structural aspects of binding of α-linked digalactosides to human galectin-1.
abstract: By definition, adhesion/growth-regulatory galectins are known for their ability to bind β-galactosides such as Galβ(1 → 4)Glc (lactose). Indications for affinity of human galectin-1 to α-linked digalactosides pose questions on the interaction profile with such bound ligands and selection of the galactose moiety for CH-π stacking. These issues are resolved by a combination of (15)N-(1)H heteronuclear single quantum coherence (HSQC) chemical shift and saturation transfer difference nuclear magnetic resonance (STD NMR) epitope mappings with docking analysis, using the α(1 → 3/4)-linked digalactosides and also Galα(1 → 6)Glc (melibiose) as test compounds. The experimental part revealed interaction with the canonical lectin site, and this preferentially via the non-reducing-end galactose moiety. Low-energy conformers appear to be selected without notable distortion, as shown by molecular dynamics simulations. With the α(1 → 4) disaccharide, however, the typical CH-π interaction is significantly diminished, yet binding appears to be partially compensated for by hydrogen bonding. Overall, these findings reveal that the type of α-linkage in digalactosides has an impact on maintaining CH-π interactions and the pattern of hydrogen bonding, explaining preference for the α(1 → 3) linkage. Thus, this lectin is able to accommodate both α- and β-linked galactosides at the same site, with major contacts to the non-reducing-end sugar unit.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Health Sciences Center, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455, USA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Miller
authors.forename: João P
authors.initials: JP
authors.lastname: Ribeiro
authors.forename: Virginia
authors.initials: V
authors.lastname: Roldós
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Martín-Santamaría
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.forename: Irina A
authors.initials: IA
authors.lastname: Nesmelova
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: Mabel
authors.initials: M
authors.lastname: Pang
authors.forename: Anatole A
authors.initials: AA
authors.lastname: Klyosov
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Mayo
mesh_terms: D001665:Binding Sites; D005697:Galactosides / Q000737:chemistry*; D037483:Galectin 1 / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
chemical_list: D005697:Galactosides; D037483:Galectin 1