title: Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides.
abstract: We have previously found by NMR and CD spectroscopic studies that the helical content of the sodium channel inactivation gate-related peptide (Ac-GGQDIFMTEEQK-NH2; MP-1A) in 80% trifluoroethanol solutions was increased by adding a pentapeptide, KIFMK. In order to study in further detail whether the presence of the IFM motif and the two lysine residues is a prerequisite for stabilizing the helical conformation, we examined interactions between various oligopeptides (RIFMR, KIFMTK, KIQMK, KAFAK, KIIIK) and MP-1A and its related peptides; that is, MP-2A in which Phe was replaced by Gln, MP-1MMA in which Thr was replaced by Met, MP-1TA in which Thr was removed from MP-1A, and MP-1A' in which L-Phe was replaced by D-Phe. It was found that the IFM motif was absolutely necessary in both the oligopeptide and the inactivation gate peptide. This finding means that hydrophobic interactions are operative between KIFMK and MP-1A. In contrast, KIFMK destabilized the helical structure of MP-1MMA, MP-1TA, and MP-1A', showing that the conformation around the IFM motif in the inactivation gate peptides is an important factor. It was concluded that the IFM motif and the two Lys residues are a prerequisite for effectively stabilizing the alpha-helix of MP-1A.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism*; D014867:Water / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D010455:Peptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C121919:lysyl-isoleucyl-phenylalanyl-methionyl-lysine; D014867:Water