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Título

Structural aspects of binding of alpha-linked digalactosides to human galectin-1

AutorMiller, Michelle C.; Ribeiro, João P.; Roldós, Virginia ; Martín-Santamaría, Sonsoles; Cañada, F. Javier ; Nesmelova, Irina V.; André, Sabine; Pang, Mabel; Klyosov, Anatole A.; Baum, Linda G.; Jiménez-Barbero, Jesús ; Gabius, Hans-Joachim; Mayo, Kevin H.
Palabras claveBovine Heart Galectin-1
Mistletoe Lectin
Ligand-Binding
Cell-Surface
Molecular-Dynamics
NMR-Spectroscopy
Animal Lectins
Cross-Linking
Force-Field
Solid-Phase
Fecha de publicacióndic-2011
EditorOxford University Press
CitaciónGlycobiology 21(12):1627-1641(2011)
ResumenBy definition, adhesion/growth-regulatory galectins are known for their ability to bind beta-galactosides such as Gal beta(1 -> 4)Glc (lactose). Indications for affinity of human galectin-1 to alpha-linked digalactosides pose questions on the interaction profile with such bound ligands and selection of the galactose moiety for CH-pi 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 alpha(1 -> 3/4)-linked digalactosides and also Gal alpha(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 alpha(1 -> 4) disaccharide, however, the typical CH-pi interaction is significantly diminished, yet binding appears to be partially compensated for by hydrogen bonding. Overall, these findings reveal that the type of alpha-linkage in digalactosides has an impact on maintaining CH-pi interactions and the pattern of hydrogen bonding, explaining preference for the alpha(1 -> 3) linkage. Thus, this lectin is able to accommodate both alpha- and beta-linked galactosides at the same site, with major contacts to the non-reducing-end sugar unit.
Descripción15 páginas, 7 figuras
Versión del editorhttp://dx.doi.org/10.1093/glycob/cwr083
URIhttp://hdl.handle.net/10261/45218
DOI10.1093/glycob/cwr083
ISSN0959-6658
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