1PX9

Solution structure of the native CnErg1 Ergtoxin, a highly specific inhibitor of HERG channel

1PX9 の概要

• エントリーDOI: 10.2210/pdb1px9/pdb
• 分子名称: ergtoxin (1 entity in total)
• 機能のキーワード: alpha/beta molecular scaffold, toxin
• 由来する生物種: Centruroides noxius (Mexican scorpion)
• 細胞内の位置: Secreted: Q86QT3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4746.41

構造登録者

Frenal, K.,Wecker, K.,Gurrola, G.B.,Possani, L.D.,Wolff, N.,Delepierre, M. (登録日: 2003-07-03, 公開日: 2004-06-22, 最終更新日: 2024-10-30)

主引用文献

Frenal, K.,Xu, C.Q.,Wolff, N.,Wecker, K.,Gurrola, G.B.,Zhu, S.Y.,Chi, C.W.,Possani, L.D.,Tytgat, J.,Delepierre, M.
Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels.
Proteins, 56:367-375, 2004

PubMed Abstract: The gamma-KTx-type scorpion toxins specific for K+ channels were found to interact with ERG channels on the turret region, while alpha-KTx3.2 Agitoxin-2 binds to the pore region of the Shaker K+ channel, and alpha-KTx5.3 BmP05 binds to the intermediate region of the small-conductance calcium-activated K-channel (SK(Ca)). In order to explore the critical residues for gamma-KTx binding, we determined the NMR structure of native gamma-KTx1.1 (CnErg1), a 42 amino acid residues scorpion toxin isolated from the venom of the Mexican scorpion Centruroïdes noxius Hoffmann, and we used computational evolutionary trace (ET) analysis to predict possible structural and functional features of interacting surfaces. The 1H-NMR three-dimensional solution structure of native ergtoxin (CnErg1) was solved using a total of 452 distance constraints, 13 3J(NH-Halpha) and 10 hydrogen bonds. The structure is characterized by 2 segments of alpha-helices and a triple-stranded antiparallel beta-sheet stabilized by 4 disulfide bridges. The ET and structural analysis provided indication of the presence of two important amino acid residue clusters, one hydrophobic and the other hydrophilic, that should be involved in the surface contact between the toxin and the channel. Some features of the proposed interacting surface are discussed.

PubMed: 15211519
DOI: 10.1002/prot.20102

実験手法

SOLUTION NMR