Active site of μ-conotoxin GIIIA, a peptide blocker of muscle sodium channels

K. Sato, Y. Ishida, K. Wakamatsu, R. Kato, H. Honda, Y. Ohizumi, H. Nakamura, M. Ohya, J. M. Lancelin, Daisuke Kohda, F. Inagaki

研究成果: ジャーナルへの寄稿記事

104 引用 (Scopus)

抄録

The amino acid sequence of μ-conotoxin GIIIA (otherwise called geographutoxin I), a peptide having 22 amino acid residues with three disulfide bridges, was modified by replacing each residue with Ala or Lys to elucidate its active center for blocking sodium channels of skeletal muscle. NMR and CD spectra were virtually identical between native and modified toxins, indicating the similarity of their conformation including disulfide bridges. The inhibitory effect of these modified peptides on twitch contractions of the rat diaphragm showed that Arg at the 13th position and the basicity of the molecule are crucial for the biological action. The segment Lys11-Asp12-Arg13 has been reported to be flexible (Lancelin, J.-M., Kohda, D., Tate, S., Yanagawa, Y., Abe, T., Satake, M., and Inagaki, F. (1991) Biochemistry, in press), and this may represent a clue for the subtle fit of Arg13 to the specific site of sodium channels. Since known ligands to sodium channels, such as tetrodotoxin, anthopleulin-A, etc., contain guanidino groups as a putative binding moiety, Arg may be a general residue for peptide toxins to interact with the receptor site on sodium channels.

元の言語英語
ページ(範囲)16989-16991
ページ数3
ジャーナルJournal of Biological Chemistry
266
発行部数26
出版物ステータス出版済み - 11 7 1991

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Conotoxins
Sodium Channel Blockers
Sodium Channels
Muscle
Catalytic Domain
Muscles
Peptides
Disulfides
Amino Acids
Biochemistry
Tetrodotoxin
Alkalinity
Diaphragms
Diaphragm
Conformations
Rats
Amino Acid Sequence
Skeletal Muscle
Nuclear magnetic resonance
Ligands

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Sato, K., Ishida, Y., Wakamatsu, K., Kato, R., Honda, H., Ohizumi, Y., ... Inagaki, F. (1991). Active site of μ-conotoxin GIIIA, a peptide blocker of muscle sodium channels. Journal of Biological Chemistry, 266(26), 16989-16991.

Active site of μ-conotoxin GIIIA, a peptide blocker of muscle sodium channels. / Sato, K.; Ishida, Y.; Wakamatsu, K.; Kato, R.; Honda, H.; Ohizumi, Y.; Nakamura, H.; Ohya, M.; Lancelin, J. M.; Kohda, Daisuke; Inagaki, F.

:: Journal of Biological Chemistry, 巻 266, 番号 26, 07.11.1991, p. 16989-16991.

研究成果: ジャーナルへの寄稿記事

Sato, K, Ishida, Y, Wakamatsu, K, Kato, R, Honda, H, Ohizumi, Y, Nakamura, H, Ohya, M, Lancelin, JM, Kohda, D & Inagaki, F 1991, 'Active site of μ-conotoxin GIIIA, a peptide blocker of muscle sodium channels', Journal of Biological Chemistry, 巻. 266, 番号 26, pp. 16989-16991.
Sato K, Ishida Y, Wakamatsu K, Kato R, Honda H, Ohizumi Y その他. Active site of μ-conotoxin GIIIA, a peptide blocker of muscle sodium channels. Journal of Biological Chemistry. 1991 11 7;266(26):16989-16991.
Sato, K. ; Ishida, Y. ; Wakamatsu, K. ; Kato, R. ; Honda, H. ; Ohizumi, Y. ; Nakamura, H. ; Ohya, M. ; Lancelin, J. M. ; Kohda, Daisuke ; Inagaki, F. / Active site of μ-conotoxin GIIIA, a peptide blocker of muscle sodium channels. :: Journal of Biological Chemistry. 1991 ; 巻 266, 番号 26. pp. 16989-16991.
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abstract = "The amino acid sequence of μ-conotoxin GIIIA (otherwise called geographutoxin I), a peptide having 22 amino acid residues with three disulfide bridges, was modified by replacing each residue with Ala or Lys to elucidate its active center for blocking sodium channels of skeletal muscle. NMR and CD spectra were virtually identical between native and modified toxins, indicating the similarity of their conformation including disulfide bridges. The inhibitory effect of these modified peptides on twitch contractions of the rat diaphragm showed that Arg at the 13th position and the basicity of the molecule are crucial for the biological action. The segment Lys11-Asp12-Arg13 has been reported to be flexible (Lancelin, J.-M., Kohda, D., Tate, S., Yanagawa, Y., Abe, T., Satake, M., and Inagaki, F. (1991) Biochemistry, in press), and this may represent a clue for the subtle fit of Arg13 to the specific site of sodium channels. Since known ligands to sodium channels, such as tetrodotoxin, anthopleulin-A, etc., contain guanidino groups as a putative binding moiety, Arg may be a general residue for peptide toxins to interact with the receptor site on sodium channels.",
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AU - Ohizumi, Y.

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AU - Inagaki, F.

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