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Structure, epitope mapping, and docking simulation of a gibberellin mimic peptide as a peptidyl mimotope for a hydrophobic ligand
Author(s) -
Murata Takashi,
Hemmi Hikaru,
Nakamura Shugo,
Shimizu Kentaro,
Suzuki Yoshihito,
Yamaguchi Isomaro
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04902.x
Subject(s) - mimotope , peptide , chemistry , docking (animal) , epitope , stereochemistry , protein structure , peptide sequence , epitope mapping , binding site , monoclonal antibody , biochemistry , biology , antibody , phage display , medicine , nursing , gene , immunology
Using NMR spectroscopy and simulated annealing calculations, we determined the solution structure of the disulfide‐linked cyclized decapeptide ACLPWSDGPC (SD), which is bound to an anti‐(gibberellin A 4 ) mAb 4‐B8(8)/E9 and was found to be the first peptidyl mimotope for a hydrophobic ligand. The resulting structure of the peptide showed a β‐turn‐like conformation in residues three to seven and the region converges well (average rmsd 0.54 Å). The binding activity and the epitopes of the peptide to the antibody were assessed using saturation transfer difference (STD)‐NMR experiments. We also conducted docking simulations between the peptide and the mAb to determine how the peptide is bound to the mAb. Resonances around the β‐turn‐like conformation of peptide SD (residues 3–5) showed strong STD enhancement, which agreed well with results from docking simulation between peptide SD and the mAb. Together with the commonality of amino acid residues of the mAb involved in interactions with gibberellin A 4 (GA 4 ) and peptide SD, we concluded that peptide SD is bound to the antigen‐binding site of mAb 4‐B8(8)/E9 as a GA 4 mimic, confirming evidence for the existence of peptide mimics even for hydrophobic ligands.