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The Galβ-(syn)-gauche configuration is required for galectin-recognition disaccharides.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2011 Jul; Vol. 1810 (7), pp. 643-51. Date of Electronic Publication: 2011 Apr 15. - Publication Year :
- 2011
-
Abstract
- Background: Galectins form a large family of animal lectins, individual members having variously divergent carbohydrate-recognition domains (CRDs) responsible for extensive physiological phenomena. Sugar-binding affinities of galectins were previously investigated by us using frontal affinity chromatography (FAC) with a relatively small set (i.e., 41) of oligosaccharides. However, total understanding of a consensus rule for galectin-recognition saccharides is still hampered by the lack of fundamental knowledge about their sugar-binding specificity toward a much larger panel of oligosaccharides in terms of dissociation constant (K(d)).<br />Methods: In the present study, we extended a FAC analysis from a more systematic viewpoint by using 142 fluorescent-labeled oligosaccharides, initially with focus on functional human galectins-1-9. Binding characteristics were further validated with 11 non-human galectins and 13 non-galectin Gal/GalNAc-binding lectins belonging to different families.<br />Results: An empirical [Galβ-equatorial] rule for galectin-recognition disaccharides was first derived by our present research and previous works by others. However, this rule was not valid for a recently reported nematode disaccharide, "Galβ1-4-L-Fuc" [Butschi et al. PLoS Pathog, 2010; 6(1):e1000717], because this glycosidic linkage was directed to 'axial' 4-OH of L-Fuc. After careful reconsideration of the structural data, we reached an ultimate rule of galectin-recognition disaccharides, which all of the galectins so far identified fulfilled, i.e., under the re-defined configuration "Galβ-(syn)-gauche". The rule also worked perfectly for differentiation of galectins from other types of lectins.<br />General Significance: The present attempt should provide a basis to solve the riddle of the glyco-code as well as to develop therapeutic inhibitors mimicking galectin ligands.<br /> (2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Binding Sites
Binding, Competitive
Chromatography, Affinity instrumentation
Disaccharides metabolism
Galectins genetics
Galectins metabolism
Humans
Molecular Structure
Oligosaccharides chemistry
Protein Binding
Protein Isoforms chemistry
Protein Isoforms genetics
Protein Isoforms metabolism
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Chromatography, Affinity methods
Disaccharides chemistry
Galectins chemistry
Molecular Conformation
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1810
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 21514365
- Full Text :
- https://doi.org/10.1016/j.bbagen.2011.04.001