Structure and Function of Cobrotoxin

Abstract

AbstractIn this review I describe the current status of the study of postsynaptic neurotoxins with special emphasis on the extensive studies of cobrotoxin which I started more than three decades ago. Cobrotoxin, is a neurotoxic protein isolated in crystalline state from the venom of Taiwan cobra Naja naja atra. It is a small basic protein consisting of a single peptide chain of 62 amino acid residues, crosslinked by four disulfide bonds. Cobrotoxin binds specifically to the nicotinic acetylcholine receptor on the postsynaptic membrane and thus blocks the neuromuscular transmission. The disulfide bonds and Tyr-25 which are buried in the molecule form a central core to maintain and stabilize the active conformation of the toxin. Selective and stepwise chemical modifications of cobrotoxin indicate that at least two cationic groups, an ϵ -amino group of Lys-47 and a guanidino group of Arg-33, both of which are common to all known postsynaptic snake neurotoxins, held at a certain critical distance in the molec...