Structure-Activity Relationship of Phospholipase A2s Isolated from Vipera aspis Venom

Aims: To elucidate the structure-activity relationship of snake venom phospholipase A2, the primary structures of two phospholipase A2s from V. aspis venom were analyzed, and the three-dimensional conformation models were compared.
Study Design: Cross-sectional study.
Place and Duration of Study: Department of Microbiology, Faculty of Pharmacy, Meijo University, between August 2009 and June 2011.
Methodology: The primary structures of purified phospholipase A2-II and -III were analyzed by Edman sequencing. Three-dimensional models of these enzymes and previously reported phospholipase A2-I (Vaspin) were constructed by the homology modeling method.
Results: Both phospholipase A2-II and –III were found to be monomeric proteins which consist of 121 and 122 amino acid residues, respectively. Their primary structures were consistent with the deduced sequence obtained from genomic DNA analysis. The molecular models of both enzymes indicated that the substitution of important amino acid residues for anticoagulant and lethal activity might have caused the relatively weak toxicity.
Conclusion: The structure-activity relationship of PLA2s was clarified by using molecular models, and clear understanding was obtained.