Amino acid sequence of a new type of toxic phospholipase A2 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, HTe, has a phospholipase A2 (PLA2) amino acid sequence. It contains 125 amino acids rather than the 119/120 found in other N. s. scutatus PLA2s, because it also has the loop of residues (62-66) found in helix D of pancreatic PLA2s, the gamma-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 HTe and other N. s. scutatus PLA2s. In the central section containing the pancreatic loop and the beta-wing, sequence similarity with other N. s. scutatus PLA2s is low. The beta-wing amino acids are highly homologous to taipoxin-gamma. HTg, an isoform of HTe, has a sequence almost identical to that of HTe in the central section. Neuropharmacological and neurophysiological studies show that HTe 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-gamma and textilotoxin-D, HTe and HTg are not glycosylated and are not otherwise modified. HTe, HTg, and the other acidic proteins hydrolyze the synthetic PLA2 substrate, 3-octanoyloxy-4-nitrobenzoic acid, as well as L-alpha-phosphatidylcholine.