Amino Acid Sequence of a New Type of Toxic Phospholipase A 2 from the Venom of the Australian Tiger Snake ( Notechis scutatus scutatus)

Abstract

Venom from the common tiger snake, Notechis scutatus scutatus, contains several toxic acidic proteins which promote hypotension and hemorrhage in mice. One of these toxins, HT e, has a phospholipase A 2 (PLA 2) amino acid sequence. It contains 125 amino acids rather than the 119/120 found in other N. s. scutatus PLA 2s, because it also has the loop of residues (62-66) found in helix D of pancreatic PLA 2s, the γ-subunit of taipoxin, and the D-subunit of textilotoxin. High sequence identity is found between the first 57 and the last 25 amino acids of HT e and other N. s. scutatus PLA 2s. In the central section containing the pancreatic loop and the β-wing, sequence similarity with other N. s. scutatus PLA 2s is low. The β-wing amino acids are highly homologous to taipoxin-γ. HT g, an isoform of HT e, has a sequence almost identical to that of HT e in the central section. Neuropharmacological and neurophysiological studies show that HT e blocks neuromuscular transmission, but it does not produce blockade by virtue of a selective action on nerve endings. Instead, the toxin acts both on nerve and on muscle. Unlike taipoxin-γ and textilotoxin-D, HT e and HT g are not glycosylated and are not otherwise modified. HT e, HT g, and the other acidic proteins hydrolyze the synthetic PLA 2 substrate, 3-octanoyloxy-4-nitrobenzoic acid, as well as L-α-phosphatidylcholine.