AskNature

“Activation of Factor X is a common point between the intrinsic and extrinsic pathway of blood coagulation [1]. Activated factor X (FXa) is the sole enzyme that catalyzes the conversion of prothrombin into thrombin, the key enzyme in the coagulation cascade; therefore inhibitors of this step are of considerable mechanistic and pharmacological interest. In addition to the two known physiological inhibitors of this serine protease, antithrombin III (AT-III) and the tissue factor pathway inhibitor (TFPI), several low molecular mass naturally occurring polypeptides inhibitors have been described, such as Antistasin, a 119-residue protein isolated from the mexican leech Haementeria offcinalis [2,3]; the tick anticoagulant peptide (TAP) [4], a 60-amino acid protein derived from the tick Ornithodoros moubata; Ecotin, a periplasmic protein found in Escherichia coli [5-7]; and the Ancylostoma caninum anticoagulant peptide (AcAP) [8]. These peptides behave as reversible, slow tight-binding inhibitors of FXa, where Antistasin and Ecotin are slowly cleaved by FXa, while TAP is not affected by the protease. Recently, we described a new natural FXa inhibitor, isolated from the saliva of the vampire bat Desmodus rotundus, which was named Draculin. Draculin is a 88.5 kDa glycoprotein which selectively inhibits both FXa and activated factor IX (FIXa) [9]. Furthermore, the anticoagulant activity of Draculin is highly dependent on the proper glycosylation of the polypeptide backbone [10]. The results described in this paper indicate that, in contrast to other natural FXa inhibitors, Draculin behaves as a noncompetitive, tight-binding inhibitor of FXa.” (Fernandez et al. 1999:135-136)