Phospholipase A2 from Crotalus atrox (PLA2)

Phospholipase A2 (PLA2) enzymes from Crotalus atrox, the Western Diamondback Rattlesnake, are critical components of its venom responsible for local and systemic toxicity (UniProt P00624). These enzymes catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids, releasing lysophospholipids and arachidonic acid, which serve as precursors for inflammatory mediators (PubMed: 27669293). In the context of envenomation, C. atrox PLA2s contribute to myotoxicity, edema, and the disruption of the coagulation cascade, leading to significant tissue damage and potential systemic complications (UniProt P00623). While traditionally viewed as toxins, they are primary targets for therapeutic intervention using polyvalent antivenoms like CroFab and small-molecule inhibitors such as Varespladib (PubChem CID 155573). Varespladib, in particular, acts by binding to the hydrophobic pocket of the enzyme, effectively blocking its catalytic activity and mitigating the downstream inflammatory and necrotic effects (PubMed: 27669293). Understanding these enzymes is vital for developing more effective treatments for rattlesnake bites and managing the associated inflammatory response. These proteins are classified into acidic and basic isoforms, each contributing differently to the overall toxic profile of the venom (UniProt P00624, P00623). Therapeutic strategies focusing on these enzymes aim to prevent the irreversible tissue damage often seen in severe envenomation cases.

Other names

Western diamondback rattlesnake venom phospholipase A2Crotalus atrox PLA2Acidic phospholipase A2Basic phospholipase A2Group IIA phospholipase A2

Inhibition of enzymatic activity by competitive binding to the active site or neutralization by antibody binding (PubMed: 27669293, CroFab Package Insert).