Precise structural determination of weakly binding peptides by utilizing dihedral angle constraints.
Structural determination of target-bound conformations of peptides is of primary importance for the optimization of peptide ligands and peptide-mimetic design. In the structural determination of weakly binding ligands, transferred nuclear Overhauser effect (TrNOE) methods have been widely used. However, not many distance constraints can be obtained from small peptide ligands by TrNOE, especially for peptides bound to a target molecule in an extended conformation. Therefore, for precise structural determination of weakly binding peptides, additional structural constraints are required. Here, we present a strategy to systematically introduce dihedral angle constraints obtained from multiple transferred cross-correlated relaxation experiments and demonstrate precise structures of weakly binding peptides. As a result, we could determine the bioactive conformations of phage-derived peptide ligands and define their core binding motifs.
Mizukoshi
Yumiko
Y
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Aomi 2-41-6, Koto-ku, Tokyo, 135-0064, Japan.
Nagasu
Michiko
M
Shimada
Ichio
I
Takahashi
Hideo
H
D016880:Anisotropy; D001665:Binding Sites; D008024:Ligands; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
D008024:Ligands; D046911:Macromolecular Substances; D010455:Peptides