Snake venom PLA₂ enzymes are esterolytic enzymes which hydrolyze glycerophospholipids at the sn-2 position of the glycerol backbone releasing lysophospholipids and fatty acids. So far, several hundred snake venom enzymes have been purified and characterized. They share similarity in structure and catalytic function with mammalian enzymes. However, in contrast to mammalian enzymes, many are toxic and induce a wide spectrum of pharmacological effects including neurotoxic (presynaptic and postsynaptic), myotoxic (local and systemic), cardiotoxic, convulsive, anticoagulant, antiplatelet and edema-inducing effects. Therefore the mechanism by which they exhibit such a variety of functions was unclear. Based on the data available in the literature, we proposed the target model. This model changed the thinking in the field and is strongly supported by experimental evidence.

• Target model – Although a variety of pharmacological effects are induced by PLA₂ enzymes, not all the effects are exhibited by all PLA₂ enzymes. Each enzyme exhibits a specific effect. To explain the susceptibility of a tissue to a particular PLA₂ enzyme, we proposed the presence of specific "target sites" on the surface of target cells or tissues. These target sites are recognized by specific "pharmacological sites" on the PLA₂ molecule. These pharmacological sites are independent of, but sometimes overlapping with, the active site of the enzyme. The target sites and pharmacological sites are complementary to each other in terms of charges, hydrophobicity and van der Waal's contact surfaces. High affinity between the target and pharmacological sites determines the specific pharmacological effects of PLA₂ enzymes. The proposed target sites could be either membrane lipids or proteins (glycoproteins). Therefore according to the target model, high affinity protein-protein interaction between PLA₂ and membrane protein in the specific target tissue determines the specific pharmacological effects of PLA₂ enzymes. We and others have shown that anticoagulant PLA₂ enzymes bind to blood coagulation factor Xa to exhibit their function (Anticoagulant phospholipase A₂enzymes).

Key Publications