Structures in Solution of Toxins from Taiwan Cobra Venom, Naja naja atra, Derived from NMR Spectra

Abstract

The structures in solution of cobrotoxin and cardiotoxins isolated from Taiwan cobra venom (Naja naja atra) were determined using 2D-NMR and simulated annealing methods. These toxins possess similar backbone conformations (a two- and a three-stranded antiparallel β sheets) with the emergence of three independent loops from the central core formed by the four disulfide bonds. Comparison of these NMR structures with the crystal structures of their homologous toxins showed good agreement except at the segments of the turns. Even though overall similarity is observed between the toxins, their functions are distinct and specific. In cobrotoxin, the electrostatic interactions of functional sites found in loops of the three-stranded β sheet cause strong binding with the receptor. In cardiotoxins, the stretches of hydrophobic residues at the tip of the flexible loops, that are surrounded by positively charged residues are expected to penetrate the lipid phase of the membrane and to form a hydrophobic cluster inside the membrane. The spatial distribution of the hydrophobic groups forms hydrophobic clusters in binding with the hydrophobic moiety of phospholipids and the spatial orientation of lysines acts as the cationic site to bind with the phosphate ion of phospholipids.