On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures

J Biol Chem. 1997 Feb 14;272(7):4302-9. doi: 10.1074/jbc.272.7.4302.


BgK is a K+ channel-blocking toxin from the sea anemone Bunodosoma granulifera. It is a 37-residue protein that adopts a novel fold, as determined by NMR and modeling. An alanine-scanning-based analysis revealed the functional importance of five residues, which include a critical lysine and an aromatic residue separated by 6.6 +/- 1.0 A. The same diad is found in the three known homologous toxins from sea anemones. More strikingly, a similar functional diad is present in all K+ channel-blocking toxins from scorpions, although these toxins adopt a distinct scaffold. Moreover, the functional diads of potassium channel-blocking toxins from sea anemone and scorpions superimpose in the three-dimensional structures. Therefore, toxins that have unrelated structures but similar functions possess conserved key functional residues, organized in an identical topology, suggesting a convergent functional evolution for these small proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Evolution*
  • Cnidarian Venoms / chemistry
  • Cnidarian Venoms / genetics*
  • Cnidarian Venoms / metabolism
  • Conserved Sequence
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Potassium Channel Blockers*
  • Protein Structure, Secondary
  • Sea Anemones
  • Sequence Homology, Amino Acid


  • Cnidarian Venoms
  • Potassium Channel Blockers
  • toxin BgK