1MB6

Three dimensional solution structure of huwentoxin-IV by 2D 1H-NMR

1MB6 の概要

• エントリーDOI: 10.2210/pdb1mb6/pdb
• NMR情報: BMRB: 5527
• 分子名称: huwentoxin-iv (1 entity in total)
• 機能のキーワード: containing a double-stranded beta-sheet and four beta-turns, toxin
• 由来する生物種: Ornithoctonus huwena (Chinese earth tiger)
• 細胞内の位置: Secreted : P83303
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4120.86

構造登録者

Peng, K.,Shu, Q.,Liang, S.P. (登録日: 2002-08-02, 公開日: 2002-08-21, 最終更新日: 2024-10-30)

主引用文献

Peng, K.,Shu, Q.,Liu, Z.,Liang, S.P.
Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena
J.Biol.Chem., 277:47564-47571, 2002

PubMed Abstract: We have isolated a highly potent neurotoxin from the venom of the Chinese bird spider, Selenocosmia huwena. This 4.1-kDa toxin, which has been named huwentoxin-IV, contains 35 residues with three disulfide bridges: Cys-2-Cys-17, Cys-9-Cys-24, and Cys-16-Cys-31, assigned by a chemical strategy including partial reduction of the toxin and sequence analysis of the modified intermediates. It specifically inhibits the neuronal tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel with the IC(50) value of 30 nm in adult rat dorsal root ganglion neurons, while having no significant effect on the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel. This toxin seems to be a site I toxin affecting the sodium channel through a mechanism quite similar to that of TTX: it suppresses the peak sodium current without altering the activation or inactivation kinetics. The three-dimensional structure of huwentoxin-IV has been determined by two-dimensional (1)H NMR combined with distant geometry and simulated annealing calculation by using 527 nuclear Overhauser effect constraints and 14 dihedral constraints. The resulting structure is composed of a double-stranded antiparallel beta-sheet (Leu-22-Ser-25 and Trp-30-Tyr-33) and four turns (Glu-4-Lys-7, Pro-11-Asp-14, Lys-18-Lys-21 and Arg-26-Arg-29) and belongs to the inhibitor cystine knot structural family. After comparison with other toxins purified from the same species, we are convinced that the positively charged residues of loop IV (residues 25-29), especially residue Arg-26, must be crucial to its binding to the neuronal tetrodotoxin-sensitive voltage-gated sodium channel.

PubMed: 12228241
DOI: 10.1074/jbc.M204063200

実験手法

SOLUTION NMR