Pharmacological and structural characterization of novel taxa-specific neurotoxins from Boiga venoms

Abstract

Snake venoms are a complex mixture of bioactive peptides and proteins that encompass an arsenal of three-finger neurotoxins. Two novel three-finger toxins, namely denmotoxin (monomer) and irditoxin (covalently-linked heterodimer) were isolated, purified and sequenced from rear-fanged colubrid snakes Boiga dendrophila and Boiga irregularis respectively. Detailed pharmacological characterization of these venom components on different vertebrate species showed high specie-specific neurotoxicity and high resolution crystal structures revealed many structurally unique features. Further, chemical synthesis of 77 amino acid residues long denmotoxin followed by the development of a refolding protocol helped to overcome its low natural abundance, while sequencing of denmotoxin gene revealed a unique organization with an additional forth exon. Present study provides the first detailed account of the structure and function of colubrid taxa-specific three-finger neurotoxins, which can contribute to greater understanding of specie-specific ligand recognition properties and function of nicotinic acetylcholine receptors.