Phospholipases A₂ of Asian Snake Venoms

Abstract

This review up-dated the structural and functional information of various phospholipase A₂ (PLA₂) isoforms purified from Asian snake venoms. A phylogenic tree of group I PLA₂s was constructed herein based on many recently resolved amino acid sequences of the venom enzymes. It was found that PLA₂s of Asian elapid venoms are structurally different from those of sea-snake/Australian elapid venoms, and are usually associated with cardiovascular effect, although exceptions such as β-bungarotoxins do exist. Two types of venom PLA₂s appear to be present in the venom of Asiatic viperinae such as Daboia and Echis, one has a N-terminal residue Asn and the other has the residue Ser. In the venom of Asiatic crotalinae, up to four subgroups of PLA₂ isoforms are present and each of them is characterized by a distinct substitution at residue 6 (Glu, Asn or Arg) or residue 49 (Asp or Lys) in their sequences. The venom PLA₂s in each of the subgroup show more or less functional similarity specific for the subgroup: the Glu6-PLA₂s are usually antiplatelet, the Asn6-PLA₂s are neurotoxic and/or myotoxic and many Arg6-PLA₂s are anticoagulating, while the Lys49-PLA₂s are myotoxic and edema-inducing. Mechanisms for the pharmacological actions of venom PLA₂s have been discussed, including neurotoxicity, myotoxicity, antiplatelet activity, anticoagulating activity, heparin-binding, protein-acylation and deacylation. Conclusions derived from many recent studies on pancreatic PLA₂ by method of protein engineering render valuable information about the structure-activity relationship of the secretory PLA₂ superfamily. Site-directed-mutagenesis methods coupled with relevant and dissecting functional assays are essential for understanding the structure-activity relationship of snake venom PLA₂s with special function or toxicity.