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Dynamic aspects of antibody:oligosaccharide complexes characterized by molecular dynamics simulations and saturation transfer difference nuclear magnetic resonance
- Source :
- Glycobiology, Glycobiology, Oxford University Press (OUP), 2011, 21 (12), pp.1570-1579. ⟨10.1093/glycob/cwr059⟩, Glycobiology, 2011, 21 (12), pp.1570-1579. ⟨10.1093/glycob/cwr059⟩
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- International audience; Carbohydrates are likely to maintain significant conformational flexibility in antibody (Ab):carbohydrate complexes. As demonstrated herein for the protective monoclonal Ab (mAb) F22-4 recognizing the Shigella flexneri 2a O-antigen (O-Ag) and numerous synthetic oligosaccharide fragments thereof, the combination of molecular dynamics simulations and nuclear magnetic resonance saturation transfer difference experiments, supported by physicochemical analysis, allows us to determine the binding epitope and its various contributions to affinity without using any modified oligosaccharides. Moreover, the methods used provide insights into ligand flexibility in the complex, thus enabling a better understanding of the Ab affinities observed for a representative set of synthetic O-Ag fragments. Additionally, these complementary pieces of information give evidence to the ability of the studied mAb to recognize internal as well as terminal epitopes of its cognate polysaccharide antigen. Hence, we show that an appropriate combination of computational and experimental methods provides a basis to explore carbohydrate functional mimicry and receptor binding. The strategy may facilitate the design of either ligands or carbohydrate recognition domains, according to needed improvements of the natural carbohydrate:receptor properties.
- Subjects :
- medicine.drug_class
Oligosaccharides
Molecular Dynamics Simulation
010402 general chemistry
Monoclonal antibody
01 natural sciences
Biochemistry
Epitope
Shigella flexneri
03 medical and health sciences
Molecular dynamics
Nuclear magnetic resonance
Antigen
medicine
Nuclear Magnetic Resonance, Biomolecular
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
MD simulations
STD-NMR
biology
MESH: Nuclear Magnetic Resonance, Biomolecular
MESH: Antibodies, Monoclonal / chemistry
MESH: Molecular Dynamics Simulation
Antibodies, Monoclonal
Oligosaccharide
O-antigen
biology.organism_classification
Ligand (biochemistry)
Affinities
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
0104 chemical sciences
chemistry
monoclonal antibody
MESH: Oligosaccharides / chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 09596658 and 14602423
- Database :
- OpenAIRE
- Journal :
- Glycobiology, Glycobiology, Oxford University Press (OUP), 2011, 21 (12), pp.1570-1579. ⟨10.1093/glycob/cwr059⟩, Glycobiology, 2011, 21 (12), pp.1570-1579. ⟨10.1093/glycob/cwr059⟩
- Accession number :
- edsair.doi.dedup.....cf0eb38683292cbab7d40671e48e6168