Anticoagulant phospholipases A2 which bind to the specific soluble receptor coagulation factor Xa

Abstract

This review will focus on Viperidae venom secreted Phospholipases A2 (sPLA2s) that exert an anticoagulant effect by a non-enzymatic, phospholipid-independent mechanism through direct binding to human coagulation factor Xa (FXa). We present the potential FXa-binding site of these anticoagulant PLA2s and the potential PLA2-binding site of FXa based on molecular docking calculations, site-directed mutagenesis and SPR affinity binding studies. We also discuss the structures of recently crystallized natural isoforms of PLA2 which interact with FXa with different affinity and which differ in anticoagulant activity. The three-dimensional structure of the PLA2 isoforms helps to explain the role of natural mutations in the binding mode of PLA2 with FXa and will be useful in structure-based design of non-competitive FXa inhibitors as potential new anticoagulant drugs.