New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.
Research output: Contribution to journal › Journal article › Research › peer-review
The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.
Original language | English |
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Journal | Journal of Biological Chemistry |
Volume | 277 |
Issue number | 45 |
Pages (from-to) | 43104-9 |
Number of pages | 5 |
ISSN | 0021-9258 |
DOIs | |
Publication status | Published - 2002 |
Bibliographical note
Keywords: Amino Acid Sequence; Binding Sites; Cation Transport Proteins; DNA-Binding Proteins; Ether-A-Go-Go Potassium Channels; Humans; Models, Molecular; Molecular Sequence Data; Plasmids; Potassium Channels; Potassium Channels, Voltage-Gated; Protein Conformation; Protein Structure, Secondary; Protein Subunits; Recombinant Proteins; Scorpion Venoms; Sequence Alignment; Sequence Homology, Amino Acid; Solutions; Substrate Specificity; Trans-Activators
ID: 8466532