Antiplatelet and anticoagulant activities of two phospholipase A2s purified from Cerastes cerastes venom: Structure‐function relationship

Abstract This study aimed to elucidate anticoagulant/antiplatelet mechanisms of two previously purified PLA 2 s from Cerastes cerastes venom, here, termed Cc 1 ‐PLA 2 and Cc 2 ‐PLA 2 . Both PLA 2 s present close molecular weights of 13,534 and 13,430 Da and Isoectric pH (pI) 7.38 and 7.86 respectively, for Cc 1 ‐PLA 2 and Cc 2 ‐PLA 2 . These Ca 2+ ‐dependent enzymes showed a high catalytic activity upon phospholipids, inducing indirect hemolysis, since they conserve the catalytic domain of PLA 2 s 26 CYCGWGGKG 34 . They exhibited dual inhibition of platelet aggregation by targeting P 2 Y 12 and TPα receptors preventing Adenosine diphosphate/arachidonate binding and blood clotting. These effects are due to the interaction of Cc 1 ‐PLA 2 s/Cc 2 ‐PLA 2 s with factor FXa through a noncatalytic PL‐independent mechanism leading to nonreleased thrombin. Both proteins consist of 120 amino acid residues and share similar three‐dimensional structures close to other SV‐PLA 2 s. Structural data of PLA 2 s allowed the relevant residues involved in binding to FXa and platelet receptors. These findings may lead to the design of novel noncompetitive FXa inhibitors.