Solution structure of discrepin, a new K+-channel blocking peptide from the alpha-KTx15 subfamily

Biochemistry. 2006 Feb 14;45(6):1795-804. doi: 10.1021/bi0519248.


Discrepin, isolated from the venom of the Venezuelan scorpion Tityus discrepans, blocks preferentially the I(A) currents of the voltage-dependent K+ channel of rat cerebellum granular cells in an irreversible way. It contains 38 amino acid residues with a pyroglutamic acid as the N-terminal residue [D'Suze, G., Batista, C. V., Frau, A., Murgia, A. R., Zamudio, F. Z., Sevcik, C., Possani, L. D., and Prestipino, G. (2004) Arch. Biochem. Biophys. 430, 256-63]. It is the most distinctive member of the alpha-KTx15 subfamily of scorpion toxins. Six members of the alpha-KTx15 subfamily have been reported so far to be specific for this subtype of the K+ channel; however, none of them have had their three-dimensional structure determined, and no information for the residues possibly involved in channel recognition and binding is available. Natural discrepin (n-discrepin) was prepared from scorpion venom, and its synthetic analogue (s-discrepin) was obtained by solid-phase synthesis. Analysis of two-dimensional 1H NMR spectra of n- and s-discrepin indicates that both peptides have the same structure. Here we report the solution structure of s-discrepin determined by NMR using 565 meaningful distance constraints derived from the volume integration of the two-dimensional NOESY spectrum, 22 dihedrals, and three hydrogen bonds. Discrepin displays the alpha/beta scaffold, characteristic of scorpion toxins. Some features of the proposed interacting surface between the toxin and channel as well as the opposite "alpha-helix surface" are discussed in comparison with those of other alpha-KTx15 members. Both n- and s-discrepin exhibit similar physiological actions as verified by patch-clamp and binding and displacement experiments.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Cerebellum / cytology
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Neurotoxins / chemistry
  • Potassium Channel Blockers / chemistry*
  • Potassium Channel Blockers / pharmacology
  • Protein Structure, Secondary
  • Rats
  • Rats, Wistar
  • Scorpion Venoms / chemistry*
  • Scorpion Venoms / isolation & purification
  • Scorpion Venoms / pharmacology


  • Neurotoxins
  • Potassium Channel Blockers
  • Scorpion Venoms
  • discrepin peptide, rat
  • discrepin protein, Tityus discrepans

Associated data

  • PDB/2AXK