A MAJOR LETHAL FACTOR OF THE VENOM OF BURMESE RUSSELLS VIPER (DABOIA-RUSSELLI-SIAMENSIS) - ISOLATION, N-TERMINAL SEQUENCING AND BIOLOGICAL-ACTIVITIES OF DABOIATOXIN

A major lethal factor, daboiatoxin (DbTx), showing strong PLA(2) activ ity (specific activity 91.7 nmoles/min/mg), was purified to homogeneit y from the venom of Burmese Russell's viper (Daboia r. siamensis) by a combination of gel filtration on Sephadex G-75 and ion-exchange chrom atography on CM-Sephadex C-25, followed by purification on high-perfor mance gel filtration Shim-pack Diol-150 column. DbTx is a single-chain PLA(2) toxin with approximate mel. wt 15,000 as determined by HPLC ge l filtration and SDS-PAGE. It constitutes 12% of total venom protein a nd is the main lethal component of Burmese Russell's viper venom with an LD(50) i.p. (0.05 mg/kg) 12-fold greater than that of the whole ven om (LD(50) i.p. 0.6 mg/kg). DbTx produces neurotoxic symptoms in mice and exhibits potent oedema-inducing activity (minimum oedema dose 0.05 mu g), indirect haemolytic activity and a strong myonecrotic activity , but no haemorrhagic activity. DbTx is cytotoxic to HeLa cells causin g cytolysis of the cells 24 hr post-exposure to toxin (50 mu g/ml). Th e first 20 N-terminal amino acid sequence (NFFQF AEMIV KMTGK EAVHS) sh ows a significant resemblance to those of the PLA(2)s from the venoms of Bulgarian viper (V. a. ammodytes) and Taiwan Russell's viper (V. r. formosensis).