Structural basis of peptide–carbohydrate mimicry in an antibody-combining site
| Autor: | Nand K. Vyas, Florante A. Quiocho, M N Vyas, Mary C. Chervenak, David R. Bundle, Pinto Bm |
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| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Stereochemistry Carbohydrates Oligosaccharides Peptide Calorimetry Crystallography X-Ray Ligands Shigella flexneri Immunoglobulin Fab Fragments Mice Molecular recognition Antigen Animals Molecule Binding site chemistry.chemical_classification Binding Sites Multidisciplinary biology Chemistry Hydrogen bond Hydrogen Bonding Biological Sciences biology.organism_classification Kinetics Binding Sites Antibody Peptides |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:15023-15028 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2431286100 |
| Popis: | The structure of a complex between the Fab fragment of the antibody (SYA/J6) specific for the cell surface O-antigen polysaccharide of the pathogenShigella flexneriY and an octapeptide (Met–Asp–Trp–Asn–Met–His–Ala–Ala), a functional mimic of the O-antigen, has been determined at 1.8-Å resolution. Comparison of the structure with that of the complex with the pentasaccharide antigen [→2)-α-l-Rha-(1→2)-α-l-Rha-(1→3)-α-l-Rha-(1→3)-β-d-GlcNAc-(1→2)-α-l-Rha-(1→] reveals the molecular recognition process by which a peptide mimics a carbohydrate in binding to an antibody. The binding modes of the two ligands differ considerably. Octapeptide binding complements the shape of the combining site groove much better than pentasaccharide binding. Moreover, the peptide makes a much greater number of contacts (126), which are mostly van der Waals interactions, with the Fab than the saccharide (74). An unusual feature is also the involvement of 12 water molecules in mediating hydrogen bonds between residues within the peptide or of the peptide and Fab. Despite better shape complementarity and greater number of contacts, the octapeptide binds with an affinity (KA= 2.5 × 105M-1, measured by calorimetry) only ≈2-fold tighter than the pentasaccharide. The structural results are relevant to the design of peptide mimetics with improved affinity for use as vaccines. |
| Databáze: | OpenAIRE |
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