Ceruleotoxin: identification in the venom of Bungarus fasciatus, molecular properties and importance of phospholipase A2 activity for neurotoxicity.
Ceruleotoxin is a potent neurotoxin which was originally purified from a batch of venom labelled Bungarus caeruleus, from the Pasteur Institute. Since NOBLE et al. have shown that this batch differs in its protein composition from that of B. caeruleus provided by Miami Serpentarium, we decided to clarify this point by comparing the composition of venoms from various Bungarus species of several origins. Although individual variations exist between samples of the same species, the venom from B. multicinctus, B. caeruleus and B. fasciatus possess characteristic protein compositions which allowed us to identify the batch used to purify ceruleotoxin as a B. fasciatus venom. We identified and purified ceruleotoxin from each of the five samples of B. fasciatus venoms tested. We failed to find this neurotoxin in either B. multicinctus or B. caeruleus venoms. Purified ceruleotoxin is a slightly basic protein with an isoelectric point of 7.4 which possesses a significant phospholipase A2 activity (200 mumoles lecithin hydrolyzed per min per mg) and a high lethal potency (i.v. LD50 in mice 0.03-0.07 mg/kg). It is composed of two identical subunits of 13,000 mol. wt. which resemble pancreas and snake venom phospholipases in their amino acid composition. Like crotoxin, ceruleotoxin irreversibly blocks the postsynaptic response of Torpedo and Electrophorus electroplaques to cholinergic agonists without preventing the binding of acetylcholine to its receptor. By hydrolyzing critical lipids of the postsynaptic membrane, it stabilizes the acetylcholine receptor - ionophore assembly in a desensitized state.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002038:Bungarotoxins / Q000032:analysis* / Q000302:isolation & purification / Q000633:toxicity; D004546:Elapid Venoms / Q000032:analysis*; D051379:Mice; D008970:Molecular Weight; D009498:Neurotoxins / Q000633:toxicity*; D010740:Phospholipases / Q000032:analysis*; D010741:Phospholipases A / Q000032:analysis*; D054467:Phospholipases A2; D011506:Proteins / Q000032:analysis
D000596:Amino Acids; D002038:Bungarotoxins; D004546:Elapid Venoms; D009498:Neurotoxins; D011506:Proteins; C014397:ceruleotoxin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2