The affinity of scorpiona-toxins for various voltage-gated sodium channels (Navs) differs considerably despite similar structures and activities. It has been proposed that key bioactive residues of the five-residue-turn (residues 8–12) and the C-tail form the NC domain, whose topology is dictated by a cis ortrans peptide-bond conformation between residues 9 and 10, which correlates with the potency on insect or mammalian Navs.