Taipoxin, an extremely potent presynaptic neurotoxin from the venom of the australian snake taipan (Oxyuranus s. scutellatus). Isolation, characterization, quaternary structure and pharmacological properties.

Taipoxin (taipan toxin), purified from the venom of the Australian taipan (Oxyuranus s. scutellatus) by gel filtration on Sephadex G-75 followed by column zone electrophoresis, is the most lethal neurotoxin yet isolated from any snake venom. The LD50 is 2 mug/kg in the mouse. The main physiological effect is a gradual reduction to complete stop of evoked and spontaneous release of acetylcholine from motor nerve terminals. Intoxicated animals die of asphyxia caused by neuromuscular blockage of the respiratory muscles. Taipoxin is a moderately acidic sialo-glycoprotein (pI 5) with a molecular weight of 45 600 as calculated from composition data or 46 800 as determined by meniscus depletion sedimentation equilibrium. Taipoxin is a 1:1:1 ternary complex of subunits designated alpha, beta and gamma which dissociate completely at low pH and high ionic strength or in 6 M guanidine hydrochloride. The dissociation by guanidine at neutral pH is reversible, while the acid-induced dissociation is not . The alpha and beta components consist of 120 amino acid residues cross-linked by seven disulfide bridges, whereas the gamma component has 135 residues and eight disulfides. The very basic (pI Greater than 10) alpha component contains 13 residues of arginine and is the only subunit displaying lethal neurotoxicity (mouse LD50 approximately 300 mug/kg). The neutral beta fraction was separated by ion-exchange chromatography into two iso-component, beta 1 and beta2, which differ slightly in amino acid composition. The very acidic gamma component contains all of the carbohydrate, which includes 4-5 residues of sialic aid. The three subunits are homologous in sequence although the gamma component is eight residues longer on the N-terminus and must also contain extra amino acids elsewhere.