Russell's viper phospholipase A2 (vvPLA2)

Russell's viper phospholipase A2 (vvPLA2) is a small, secreted, calcium-dependent enzyme (13–18 kDa) found in the venom of Daboia russelii (Russell’s viper). It belongs to the group IIA secreted phospholipase A2 family and is stabilized by 6–7 disulfide bonds[1][2][3]. Structurally, the enzyme features an N-terminal alpha helix, two disulfide-connected alpha helices (housing the catalytic dyad His48/Asp49), a double-stranded antiparallel beta-sheet, a calcium-binding loop, and a flexible C-terminal loop[1][2][3]. vvPLA2 hydrolyzes the sn-2 acyl bond of membrane phospholipids, releasing fatty acids and lysophospholipids, thereby disrupting cell membranes. Variants of this enzyme (acidic and basic isoforms) display differences in toxicity, with basic forms being more toxic due to higher affinity for cellular membranes[2]. This enzyme contributes to a range of toxic manifestations in envenomation, including hemostatic disturbances, cytotoxicity, neuromuscular impairment, and inflammation. There is active interest in developing antivenoms and small-molecule inhibitors to neutralize PLA2-mediated toxicity, though structural diversity poses notable therapeutic challenges[1][2].

Other names

Snake venom phospholipase A2 (from Russell's viper)viper venom PLA2Daboia russelii phospholipase A2Group IIA secreted phospholipase A2

Hydrolysis of sn-2 position in phospholipids, leading to production of lysophospholipids and fatty acids, which disrupts cellular membranes and induces cytotoxicity[1][2][3]. Calcium-dependent enzyme catalysis requiring a cofactor and a conserved catalytic dyad (His48/Asp49)[1][2][3]. Some basic vvPLA2s act through direct cytolytic, anticoagulant, or neurotoxic mechanisms[2][4].