STRUCTURES IN SOLUTION OF TOXINS FROM TAIWAN COBRA VENOM, NAJA-NAJA-ATRA, DERIVED FROM NMR-SPECTRA

The structures in solution of cobrotoxin and cardiotoxins isolated fro m Taiwan cobra venom (Naja naja ah a) were determined using 2D-NMR and simulated annealing methods. These toxins possess similar backbone co nformations (a two- and a three-stranded antiparallel beta sheets) wit h the emergence of three independent loops from the central core forme d by the four disulfide bonds. Comparison of these NMR structures with the crystal structures of their homologous toxins showed good agreeme nt except at the segments of the turns. Even though overall similarity is observed between the toxins, their functions are distinct and spec ific. In cobrotoxin, the electrostatic interactions of functional site s found in loops of the three-stranded beta sheet cause strong binding with the receptor. In cardiotoxins, the stretches of hydrophobic resi dues at the tip of the flexible loops, that are surrounded by positive ly charged residues are expected to penetrate the lipid phase of the m embrane and to form a hydrophobic cluster inside the membrane. The spa tial distribution of the hydrophobic groups forms hydrophobic clusters in binding with the hydrophobic moiety of phospholipids and the spati al orientation of lysines acts as the cationic site to bind with the p hosphate ion of phospholipids.