Draculin, the anticoagulant factor in vampire bat saliva, is a tight-binding, noncompetitive inhibitor of activated factor X

Biochim Biophys Acta. 1999 Sep 14;1434(1):135-42. doi: 10.1016/s0167-4838(99)00160-0.


The kinetic mechanism of action of Draculin on activated Factor X (FXa) is established. Draculin inhibits activated Factor X within seconds of incubation at near equimolar concentration (2-6 times on molar basis). Fitting the data to the equation for a tight-binding inhibitor gives a value for K(i)(K(d)) = 14.8+/-1.5 nM. The formation of the Draculin-FXa complex can be explained by a two-step mechanism, where for the first, reversible step, k(on) = 1.117 (+/- 0.169, S.E.M.) x 10(6) M(-1)s(-1) and k(off) = 15.388 (+/- 1.672) x 10(-3) s(-1), while for the second, irreversible step, which is concentration-independent, k(2) = 0.072 s(-1). K(d) obtained from k(off)/k(on) = 13.76 nM. Lineweaver-Burk plot shows a noncompetitive behavior. This noncompetitive mode of inhibition of Draculin is supported by the observation that Draculin, at concentrations giving complete inhibition, does not impair binding of p-aminobenzamidine to FXa. Moreover, under the same conditions, Draculin induces <14% decrease of the fluorescence intensity of the p-aminobenzamidine-FXa complex. We conclude that Draculin is a noncompetitive, tight-binding inhibitor of FXa, a characteristic so far unique amongst natural FXa inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / chemistry*
  • Benzamidines / chemistry
  • Chiroptera
  • Chromatography, High Pressure Liquid
  • Factor Xa Inhibitors*
  • Glycoproteins / chemistry*
  • Kinetics
  • Protein Binding
  • Saliva / chemistry*
  • Salivary Proteins and Peptides / chemistry*


  • Anticoagulants
  • Benzamidines
  • Factor Xa Inhibitors
  • Glycoproteins
  • Salivary Proteins and Peptides
  • draculin
  • 4-aminobenzamidine