A case study of cardiotoxin III from the Taiwan cobra (Naja naja atra). Solution structure and other physical properties.

Abstract

Snake venoms are a mixture of many different toxins of which the cardiotoxins and the neurotoxins are the most toxic (1,2). The cardiotoxins and the neurotoxins (long and short), isolated from different snake venom species belonging to the Elapidae family show significant amount of homology (50–60%) in their primary amino acid sequences (3,4). More generally, cardiotoxins and neurotoxins belong structurally to the three-finger proteins, which also includes other proteins such as wheat germ agglutinin (5,6). The members of these toxin groups are small molecular weight proteins (6–7.5 Kda) with 60–75 amino acids (7). The primary structure homology between these two toxins groups includes similar location of the disulfide bridges (8). Despite the homology in their primary amino acid sequences, cardiotoxins and the neurotoxins, show drastically different biological activities. The target of neurotoxins is well identified as the nicotinic acetylcholine receptor at the post–synaptic level of the neuro-muscular junction (9,10). Even if a detailed mechanism is not known, it is clear that the function of neurotoxins is to block the receptor and thus prevent binding of acetylcholine receptor (11,12). By contrast, little is known about the mode of action of cardiotoxins (13). The cardiotoxins elicit depolarization and contraction of muscular cells, loss of excitability and depolarization of nervous cells (14). They are also known to prevent aggregation by lytic effect on platelets (15). Various types of cells like erythrocytes, epithelial cells and fetal lung cells are also known to lyse at higher concentrations of cardiotoxins (16–18). The mechanism of the lytic action of cardiotoxins is still controversial (19).