1. Structural aspects of binding of α-linked digalactosides to human galectin-1
- Author
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Miller, Michelle C, Ribeiro, João P, Roldós, Virginia, Martín-Santamaría, Sonsoles, Cañada, F Javier, Nesmelova, Irina A, André, Sabine, Pang, Mabel, Klyosov, Anatole A, Baum, Linda G, Jiménez-Barbero, Jesús, Gabius, Hans-Joachim, and Mayo, Kevin H
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Brain Disorders ,Infectious Diseases ,Generic health relevance ,Affordable and Clean Energy ,Binding Sites ,Galactosides ,Galectin 1 ,Humans ,Hydrogen Bonding ,Models ,Molecular ,Molecular Conformation ,Molecular Dynamics Simulation ,agglutinin ,glycolipid ,glycoprotein ,lectin ,sugar code ,Medical and Health Sciences ,Biochemistry & Molecular Biology ,Biochemistry and cell biology - 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.
- Published
- 2011