Catalytically Active Snake Venom PLA₂ Enzymes: An Overview of Its Elusive Mechanisms of Reaction

Abstract

Snake venom-secreted phospholipase A 2 (svPLA 2 ) 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 2 are still to be thoroughly understood. This review presents and analyses the most plausible reaction mechanisms for svPLA 2, such as the "single-water mechanism" or the "assisted-water mechanism" initially proposed for the homologous human PLA 2 . All of the mechanistic possibilities are characterized by a highly conserved Asp/His/water triad and a Ca 2+ cofactor. The extraordinary increase in activity induced by binding to a lipid−water interface, known as "interfacial activation," critical for the PLA 2 s activity, is also discussed. Finally, a potential catalytic mechanism for the postulated noncatalytic PLA 2 -like proteins is anticipated.

Viper Venom Phospholipase A2 Database: The Structural and Functional Anatomy of a Primary Toxin in Envenomation

“…The Ca 2+ -coordinating Asp49 is replaced by a Lys residue in 68% of the database PLA2-like proteins ( Figure 5 B) and by a Ser, Asn, Gln, or Arg in the remaining cases. The catalytic machinery is essentially preserved in the PLA2-like proteins, supporting the hypothesis that the latter can catalyze the breaking of the sn-2 bond but become inactivated due to inefficient product release [ 33 ].…”

“…Following the ester bond cleavage, the hydrolyzed products—fatty acid and lysophospholipid—are released ( Figure 2 C). No evidence exists for protein conformational changes during the cycle [ 33 ].…”

Bacterial model membranes under the harsh subsurface conditions of Mars

“…Finally, to demonstrate how the presence of the Mars-relevant salts in combination with high hydrostatic pressure can modulate biologically relevant reactions, the kinetics of the hydrolysis of phospholipids operated by the bee venom phospholipase A2 (PLA2) was monitored. 17,29 PLA2 is an esterase which is able to catalyse the hydrolysis of membrane glycerophospholipids at the sn -2 position leading to the formation of a free fatty acid and lysophospholipid (which contains only one hydrophobic chain) (Fig. 5(A)).…”

Proteotransciptomics of the Most Popular Host Sea Anemone Entacmaea quadricolor Reveals Not All Toxin Genes Expressed by Tentacles Are Recruited into Its Venom Arsenal

“…However, the E. quadricolor PLA2 shares 38% amino acid identity and 47% amino acid similarity with a PLA2 protein found in the Australian taipan snake, Oxyuranus scutellatus’ venom been shown to have neurotoxicity and myotoxicity [ 45 , 46 ]. The PLA2 in E. quadricolor venom is probably catalytically active as it contains the His48/Asp99 dyad at the active site [ 47 ], but it lacks the C-terminal extension region that has been shown to be responsible for myotoxic effects ( Figure S4 ).…”