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

This study aimed to elucidate anticoagulant/antiplatelet mechanisms of two previously purified PLA s from Cerastes cerastes venom, here, termed Cc -PLA and Cc -PLA . Both PLA s present close molecular weights of 13,534 and 13,430 Da and Isoectric pH (pI) 7.38 and 7.86 respectively, for Cc -PLA and Cc -PLA . These Ca -dependent enzymes showed a high catalytic activity upon phospholipids, inducing indirect hemolysis, since they conserve the catalytic domain of PLA s CYCGWGGKG . They exhibited dual inhibition of platelet aggregation by targeting P Y and TPα receptors preventing Adenosine diphosphate/arachidonate binding and blood clotting. These effects are due to the interaction of Cc -PLA s/Cc -PLA 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 s. Structural data of PLA 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.