5DO6

Crystal structure of Dendroaspis polylepis venom mambalgin-1 T23A mutant

5DO6 の概要

• エントリーDOI: 10.2210/pdb5do6/pdb
• 関連するPDBエントリー: 2MFA 2MJY
• 分子名称: Mambalgin-1, IODIDE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: toxin, acid sensing ion channels, pain suppression drug, elapid venom polypeptide
• 由来する生物種: Dendroaspis polylepis polylepis (Black mamba)
• 細胞内の位置: Secreted : P0DKR6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13861.92

構造登録者

Stura, E.A.,Tepshi, L.,Kessler, P.,Gilles, M.,Servent, D. (登録日: 2015-09-10, 公開日: 2015-12-30, 最終更新日: 2024-10-23)

主引用文献

Mourier, G.,Salinas, M.,Kessler, P.,Stura, E.A.,Leblanc, M.,Tepshi, L.,Besson, T.,Diochot, S.,Baron, A.,Douguet, D.,Lingueglia, E.,Servent, D.
Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition.
J.Biol.Chem., 291:2616-2629, 2016

PubMed Abstract: Mambalgins are peptides isolated from mamba venom that specifically inhibit a set of acid-sensing ion channels (ASICs) to relieve pain. We show here the first full stepwise solid phase peptide synthesis of mambalgin-1 and confirm the biological activity of the synthetic toxin both in vitro and in vivo. We also report the determination of its three-dimensional crystal structure showing differences with previously described NMR structures. Finally, the functional domain by which the toxin inhibits ASIC1a channels was identified in its loop II and more precisely in the face containing Phe-27, Leu-32, and Leu-34 residues. Moreover, proximity between Leu-32 in mambalgin-1 and Phe-350 in rASIC1a was proposed from double mutant cycle analysis. These data provide information on the structure and on the pharmacophore for ASIC channel inhibition by mambalgins that could have therapeutic value against pain and probably other neurological disorders.

PubMed: 26680001
DOI: 10.1074/jbc.M115.702373

実験手法

X-RAY DIFFRACTION (1.697 Å)