tailieunhanh - Báo cáo khoa học: Structure, epitope mapping, and docking simulation of a gibberellin mimic peptide as a peptidyl mimotope for a hydrophobic ligand

Using NMR spectroscopy and simulated annealing calculations, we deter-mined the solution structure of the disulfide-linked cyclized decapeptide ACLPWSDGPC (SD), which is bound to an anti-(gibberellin A4) mAb 4-B8(8)⁄E9 and was found to be the first peptidyl mimotope for a hydro-phobic ligand. The resulting structure of the peptide showed ab-turn-like conformation in residues three to seven and the region converges well (average rmsd A ˚ ). | iFEBS Journal Structure epitope mapping and docking simulation of a gibberellin mimic peptide as a peptidyl mimotope for a hydrophobic ligand Takashi Murata1 3 Hikaru Hemmi1 Shugo Nakamura2 Kentaro Shimizu2 Yoshihito Suzuki3 and Isomaro Yamaguchi3 1 NationalFood Research Institute Kannondai Tsukuba Japan 2 Department of Biotechnology Division of Agriculture and AgriculturalLife Sciences The University of Tokyo Japan 3 Department of Applied BiologicalChemistry Division of Agriculture and AgriculturalLife Sciences The University of Tokyo Japan Keywords solution structure STD-NMR docking simulation hydrophobic ligand mimic peptide Correspondence H. Hemmi NationalFood Research Institute 2-1-12 Kannondai Tsukuba Ibaraki 305-8642 Japan Fax 81 29 8387996 Tel 81 29 8388033 E-mail hemmi@ Note The atomic coordinates for the 50 conformers of peptide SD described in this paper have been deposited with the Protein Data Bank PDB ID 1YT6 . Chemical shifts for peptide SD have been deposited in the BioMagRes Bank as entry 6511. Received 9 June 2005 revised 29 July 2005 accepted 4 August 2005 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 A4 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 b-turn-like conformation in residues three to seven and the region converges well average rmsd A . 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 b-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. .