Scorpion venoms are complex mixtures of neurotoxins (low molecular weight proteins), cardiotoxins, hemolytic toxins, antimicrobial peptides, enzymes (such as hyaluronidase, acetylcholinesterase, phospholipase and metalloproteinases), lipides, nucleotides, mucopolysaccharides and biogenic amines. Neurotoxins can be classified as either short- or long-chain toxins, which share a common structural motif, named CS-α/β for cysteine-stabilized α-helix/β-sheet. Short-chain neurotoxins (SCNs) usually contain 30-40 residues and three or four disulphide bridges. Most of the short chain toxins block voltage-dependent or Ca(2+)-activated K(+) channels. Most long-chain neurotoxins (LCNs) are composed of 60-70 residues and are cross-linked by four disulphide bridges. The long chain or voltage-gated sodium channels scorpion neurotoxins (NaScTxs) can be classified either as α-toxins, which slow down Na(+) channel inactivation, or β-toxins, which affect the channel activation process. Both types make the inactivation of the sodium channel incomplete [1,2,3]. Neurotoxins of the birtoxin family can be included in the group of LCNs, although they possess three disulfide bridges instead of the usual four disulfide bridges of other members of the group and they are uniquely shorter than other LCNs [4,5].

The LCN-type CS-α/β domain consists of one or two short segments of α-helix plus a triple-stranded β-sheet, connected by variable regions forming loops (turns) (see <PDB:1B3C>) [6]. The β-sheet and the α-helix are held together by two disulfide bridges.

The profile we developed covers the entire LCN-type CS-α/β domain.