1PX9

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

Summary for 1PX9

• Entry DOI: 10.2210/pdb1px9/pdb
• Descriptor: ergtoxin (1 entity in total)
• Functional Keywords: alpha/beta molecular scaffold, toxin
• Biological source: Centruroides noxius (Mexican scorpion)
• Cellular location: Secreted: Q86QT3
• Total number of polymer chains: 1
• Total formula weight: 4746.41

Authors

Frenal, K.,Wecker, K.,Gurrola, G.B.,Possani, L.D.,Wolff, N.,Delepierre, M. (deposition date: 2003-07-03, release date: 2004-06-22, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

SOLUTION NMR