Structure and functions of coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis.

Abstract

Snake venoms contain various anticoagulants that affect blood coagulation system (1, 2). The anticoagulant is classified into two categories: anticoagulant enzymes and non-enzymatic anticoagulants. The examples of the former category are phospholipases, fibrinogenolytic enzymes, protein C activators, and proteolytic enzymes that convert coagulation factors into degraded inactive forms. An interesting example of the non-enzymatic anticoagulants is an inhibitor of the activation of prothrombin. The inhibitors in this category have been first found in the venom of Agkistrodon acutus (3) and Trimeresurus gramineus (4). The anticoagulant protein isolated from A. acutus inhibits the participation of factor Xa in the prothrombinase complex formation (5, 6). In order to understand the anticoagulant mechanism we have isolated and characterized another anticoagulant protein with Mr 27,000 from the venom of the habu snake Trimeresurus flavoviridis (7). This anticoagulant protein forms a complex with either coagulation factor IX or factor X with a stoichiometry of 1 to 1 in a calcium-dependent fashion, and thereby blocks the amplification of the coagulation cascade (7). Thus, we named it IX/X-bp (factor IX/factor X-binding protein). This chapter describes the structural and functional properties of IX/X-bp from the venom of the habu snake (T. flavoviridis).