Catalytically Active Snake Venom PLA Enzymes: An Overview of Its Elusive Mechanisms of Reaction.

Snake venom-secreted phospholipase A (svPLA) enzymes, both catalytically active and inactive, are a central component in envenoming. These are responsible for disrupting the cell membrane's integrity, inducing a wide range of pharmacological effects, such as the necrosis of the bitten limb, cardiorespiratory arrest, edema, and anticoagulation. Although extensively characterized, the reaction mechanisms of enzymatic svPLA are still to be thoroughly understood. This review presents and analyses the most plausible reaction mechanisms for svPLA such as the "single-water mechanism" or the "assisted-water mechanism" initially proposed for the homologous human PLA. All of the mechanistic possibilities are characterized by a highly conserved Asp/His/water triad and a Ca cofactor. The extraordinary increase in activity induced by binding to a lipid-water interface, known as "interfacial activation," critical for the PLAs activity, is also discussed. Finally, a potential catalytic mechanism for the postulated noncatalytic PLA-like proteins is anticipated.