The solution structure of BmK alpha Tx11 presented by this paper is distinctive from any other structures of wide-type scorpion alpha-toxins reported so far, for its trans-9,10 peptide bond conformation is accompanied by 'protruding' topology of the 'NC-domain'. The orientation of the C-tail of BmK alpha Tx11 is obviously different from that of classical alpha-toxins (e g., AaH2, BmK-M8), despite the fact that they share common trans conformation of peptide bond between residues 9 and 10 Accordingly, there must be other structural factors dominating the orientation of the C-tail except the conformation of peptide bond 9-10. Our study reveals that residues at position 58 play an important role in it, and different type of residues at this position (e g.. Lys. Arg, Met, Ile) result in different spatial relationship between the C-terminus and the 'five-residue-turn' and then different topology of the 'NC-domain', therefore residues at position 58 are believed to function as structure and bioactivity switch for specificity of scorpion alpha-toxins The mechanism for stabilizing the geometry of the 'NC-domain' in wide-type scorpion alpha-toxins is also discussed (C) 2009 Elsevier Inc. All rights reserved