INHIBITION OF PROTEIN-KINASE-C BY SNAKE VENOM TOXINS - COMPARISON OF ENZYME-INHIBITION, LETHALITY AND HEMOLYSIS AMONG DIFFERENT CARDIOTOXINISOFORMS

Cardiotoxins, neurotoxins and phospholipase A(2) (PLA(2)) are three ma jor classes of toxic components present in the Taiwan cobra, Naja naja atra of the Elapidae family. Cardiotoxins (or called cytotoxins), a g roup of major polypeptides of around 60 amino-acid residues present ab undantly in the elapid family of snakes, comprise about 45-55% in the crude venom of Taiwan cobra. In contrast to another prominent group of structurally similar neurotoxins with well-established acetylcholine receptors and modes of action, cardiotoxins showed no defined cellular targets and very diverse pharmacological functions. A systematic stru cture/function comparison of these toxins was made by their relative i nhibitory effects on protein kinase C (PKC) isolated from mouse brains . Lethality and hemolysis of various cardiotoxin isoforms were also co mpared in order to shed some insight on the biological targets and mec hanisms of these surface-active amphiphilic polypeptides. A structure comparison of these cardiotoxins based on computer model building reve aled that some defined and subtle differences can be detected upon the superposition of these three-dimensional polypeptide chains, which ma y reflect the intrinsic differences in the hydrophobic peptide segment s present on the surface loops of toxin molecules. The differences see m to correlate with different inhibitory activities exhibited by cardi otoxins in contrast to the lack of activity by cobrotoxin and PLA(2) o n PKC.