An NMR conformational analysis of a synthetic peptide Cn2(1-15)NH2S-S-acetyl-Cn2(52-66)NH2 from the New World Centruroides noxius 2 (Cn2) scorpion toxin: Comparison of the structure with those of the Centruroides scorpion toxins

The solution structure of a synthetic peptide, Cn2(1-15)NH2-S-S-acetyl-Cn2( 52-66)NH2 from toxin 2 (Cn2) of the New World scorpion Centruroides noxius was determined using nmr and molecular dynamics calculations. The peptide h as no significant secondary structure such as nn a-helix ol a beta-sheer, y et it has a fixed conformation for the first chain. The backbone secondary structure involving residues 6-12 in this peptide shows an excellent overla p with the structures of natural neurotoxins from Centruroides sculpturatus Ewing. Residues 6-9 form a distorted type I beta-turn and residues 10-12 S onn a gamma-turn. As residues 7-10 in the Centruroides toxins correspond to one of the regions of highest sequence variability it may account for rite species specificity and/or selectivity of toxic action. The conformation o f this region evidently plays all important role ill receptor recognition a nd in binding to the neutralizing monoclonal antibody BCFS raised against t he intact toxin. (C) 1999 John Wiley & Sons, Inc.