New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1

Yuliya V. Korolkova, Eduard V. Bocharov, Kamilla Angelo, Innokenty V. Maslennikov, Olga V. Grinenko, Aleksey V. Lipkin, Elena D. Nosyreva, Kirill A. Pluzhnikov, Søren Peter Olesen, Alexander S. Arseniev, Eugene V. Grishin

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Abstract

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 α-helix and a triple-stranded antiparallel β-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 α-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the β-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.

Original languageEnglish (US)
Pages (from-to)43104-43109
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number45
DOIs
StatePublished - Nov 8 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Korolkova, Y. V., Bocharov, E. V., Angelo, K., Maslennikov, I. V., Grinenko, O. V., Lipkin, A. V., Nosyreva, E. D., Pluzhnikov, K. A., Olesen, S. P., Arseniev, A. S., & Grishin, E. V. (2002). New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1. Journal of Biological Chemistry, 277(45), 43104-43109. https://doi.org/10.1074/jbc.M204083200