INTERACTION OF SNAKE-VENOM PROTEINS WITH BLOOD COAGULATION FACTORS: MECHANISMS OF ANTICOAGULANT ACTIVITY

Abstract

Snake venoms are rich in a large variety of proteins and peptides that can interfere with the hemostatic system. This review focuses on snake-venom proteins, with or without enzymatic activity, that bind to blood coagulation factors and exhibit anticoagulant effects. These proteins include (1) anticoagulant phospholipases A2, which bind to factor X and impair the formation of prothrombinase complex independently from their enzymatic activity; (2) factor IX- and X-binding proteins, which belong to the family of C-type lectin-like proteins and interact with the Gla domain of factor X/Xa and/or IX/IXa; (3) prothrombin- and thrombin-binding proteins, represented by bothrojaracin and salmorin, which are also C-type lectin-like molecules and either bind to prothrombin, impairing thrombin formation, or to thrombin, inhibiting its biological activities, such as clotting of fibrinogen, platelet activation, and so forth; and (4) L-amino oxidases that have recently been described to have anticoagulant activity. The general structural characteristics of these proteins and current knowledge regarding their mechanisms of action are discussed. These proteins have helped in our understanding of some molecular aspects of the hemostatic process. A more detailed analysis of the structure–function relationship of these molecules will certainly result in new medical and pharmacological applications. Furthermore, venom components offer attractive templates for the development of rationally designed therapeutic agents.