Bothrojaracin – A Potent Thrombin Inhibitor

  • Russolina B. ZingaliEmail author
  • Ana Cristina Ferraz Nogueira


Snake venoms are rich in a large variety of proteins and peptides that can interfere with the hemostatic system. This review focuses on bothrojaracin, which is snaclec molecule, either bind to thrombin, inhibiting its biological activities, such as clotting of fibrinogen, platelet activation or to prothrombin, impairing thrombin formation. Bothrojaracin interacts with both molecules, forming a stable 1:1 complex. The calculated Kd for bothrojaracin was 0.6 nM and 100 nM for thrombin and prothrombin, respectively. Bothrojaracin binds to thrombin exosite I displacing ligands such as fibrin, hirudin, thrombomodulin and factor V and do not block the catalytic site. This protein has helped in our understanding of some molecular aspects of the thrombin and prothrombin structure–function relationship. The knowledge about the mechanism of action and details of structural aspects will certainly result in new medical and pharmacological applications. Furthermore, bothrojaracin offer attractive template for the development of rationally designed therapeutic agents.


Snake Venom Hemostatic System Factor Versus Activation Fibrinogen Clotting Thrombin Specific Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Arocas, V., Zingali, R.B., Guillin, M.C., Bon, C., Jandrot-Perus, M., 1996. Bothrojaracin: a potent two-site-directed thrombin inhibitor. Biochemistry 35, 9083–9089.PubMedCrossRefGoogle Scholar
  2. Arocas, V., Castro, H.C., Zingali, R.B., Guillin, M.C., Jandrot-Perrus, M., Bon, C., Wisner, A., 1997. Molecular cloning and expression of bothrojaracin, a potent thrombin inhibitor from snake venom. Eur. J. Biochem. 248, 550–557.PubMedCrossRefGoogle Scholar
  3. Arocas, V., Lemaire, C., Bouton, M.C., Beazeaud, A., Bon, C., Guillin, M.C., Jandrot-Perrus, M., 1998. Inhibition of thrombin-catalysed factor V activation by bothrojaracin. Thromb. Haemost. 79, 1157–1161.PubMedGoogle Scholar
  4. Assafim, M., Ferreira, M.S., Frattani, F.S., 2006. Counteracting effect of glycyrrhizin on the hemostatic abnormalities induced by Bothrops jararaca snake venom. Br. J. Pharmacol. 148, 807–813.PubMedCrossRefGoogle Scholar
  5. Atoda, H., Morita, T., 1989. A novel blood coagulation factor IX/factor X518 binding protein with anticoagulant activity from the venom of Trimeresurus flavoviridis (Habu snake): isolation and characterization. J. Biochem. 106, 808–813.PubMedGoogle Scholar
  6. Atoda, H., Hyuga, M., Morita, T., 1991. The primary structure of coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Homology with asialoglycoprotein receptors, proteoglycan core protein, tetranectin, and lymphocyte Fc epsilon receptor for immunoglobulin. J. Biol. Chem. 266, 14903–14911.PubMedGoogle Scholar
  7. Atoda, H., Ishikawa, M., Yoshihara, E., Sekiya, F., Morita, T., 1995. Blood coagulation factor IX-binding protein from the venom of Trimeresurus flavoviridis: purification and characterization. J. Biochem. 118, 965–973.PubMedCrossRefGoogle Scholar
  8. Atoda, H., Ishikawa, M., Mizuno, H., Morita, T., 1998. Coagulation factor X binding protein from Deinagkistrodon acutus venom is a Gla domain-binding protein. Biochemistry 37, 17361–17370.PubMedCrossRefGoogle Scholar
  9. Atoda, H., Kaneko, H., Mizuno, H., Morita, T., 2002. Calcium-binding analysis and molecular modeling reveal Echis coagulation factor IX/factor X binding protein has the Ca-binding properties and Ca ion-independent folding of other C-type lectin-like proteins. FEBS Lett. 531, 229–234.PubMedCrossRefGoogle Scholar
  10. Bode, W., 2006. The structure of thrombin: a janus-headed proteinase. Sem. Throm. Hem. 32, 16–31.CrossRefGoogle Scholar
  11. Boffa, G.A., Boffa, M.C., Winchenne, J.J., 1976. A phospholipase A2 with anticoagulant activity. Isolation from Vipera berus venom and properties. Biochem. Biophys. Acta 429, 839–852.PubMedCrossRefGoogle Scholar
  12. Braud, S., Bon, C., Wisner, A., 2000. Snake venom proteins acting on hemostasis. Biochimie 82, 851–859.PubMedCrossRefGoogle Scholar
  13. Bukys, M.A., Orban, T., Kim, P.Y. Beck, D.O., Nesheim, M.E., Kalafatis, M., 2006. The structural integrity of anion binding exosite of thrombin is required and sufficient for timely cleavage and activation of factor V and factor VIII. J. Biol. Chem. 281, 18569–18580.PubMedCrossRefGoogle Scholar
  14. Castro, H.C., Dutra, D.L.S., Oliveira-Carvalho, A.L., Zingali, R.B., 1998. Bothroalternin, a thrombin inhibitor from the venom of Bothrops alternatus. Toxicon 36, 1903–1912.PubMedCrossRefGoogle Scholar
  15. Castro, H.C., Rodrigues, C.R., 2006. Current status of snake venom thrombin-like enzymes. Toxin Rev. 25, 291–318.CrossRefGoogle Scholar
  16. Castro, H.C., Zingali, R.B., Albuquerque, M.G., Pujol-luz, M., Rodrigues, C.R., 2004. Snake venom thrombin-like enzymes: from reptilase to now. Cell. Mol. Life Sci. 61, 843–856.PubMedCrossRefGoogle Scholar
  17. Chen, Y.L., Tsai, I.H., 1996. Functional and sequence characterization of coagulation factor IX/factor X-binding protein from the venom of Echis carinatus leucogaster. Biochemistry 35, 5264–5271.PubMedCrossRefGoogle Scholar
  18. Chippaux, J., Williams, V., White, J., 1991. Snake venom variability: methods of study results and interpretation. Toxicon 29, 1279–1303.PubMedCrossRefGoogle Scholar
  19. Clemetson, K.J., Morita, T., Kini, R.M., 2009. Scientific and standardization committee communications: classification and nomenclature of snake venom C-type lectins and related proteins. J. Thromb. Haemost. 7, 360.PubMedCrossRefGoogle Scholar
  20. Cox, A.C., 1993. Coagulation factor X inhibitor from hundred-pace snake (Deinagkistrodon acutus) venom. Toxicon 31, 1445–1457.PubMedCrossRefGoogle Scholar
  21. Davie, E.W., Fujikawa, K., Kisiel, W., 1991. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363–10370.PubMedCrossRefGoogle Scholar
  22. Electricwala, A., von Sicard, N.A.E., Sawyer, R.T., Atkinson, T., 1993. Biochemical characterisation of a pancreatic elastase inhibitor from the leech Hirudinaria manillensis. J. Enzyme Inhib. 6, 293–302.CrossRefGoogle Scholar
  23. Esmon, C.T., Lollar, P., 1996. Involvement of thrombin anion-binding exosites 1 and 2 in the activation of factor V and factor VIII. J. Biol. Chem. 271, 13882–13887.PubMedCrossRefGoogle Scholar
  24. Fareed, J., Lewis, B.E., Callas, D.D., Hoppensteadt, D.A., Walenga, J.M., Bick, R.L., 1999. Antithrombin agents: the new class of anticoagulant and antithrombotic drugs. Clin. Appl. Thromb. Hemost. 5, S45–S55.PubMedCrossRefGoogle Scholar
  25. Fox, J.W., Serrano, S.M.T., 2009. Timeline of key events in snake venom metalloproteinase research. J. Proteomics 72, 200–209.PubMedCrossRefGoogle Scholar
  26. Francischetti, I.M., Gombarovits, M.E., Valenzuela, J.G., Carlini, C.R., Guimarães, J.A., 2000. Intraspecific variation in the venoms of the South American rattlesnake (Crotalus durissus terrificus). Comp. Biochem. Physiol. C. 127, 23–36.Google Scholar
  27. Friedrich, T., Kroger, B., Bialojan, S., Lemaire, H.G., Hoffken, H.W., Reuschenbach, P., Otte, M., Dodt, J., 1993. A kazal-type inhibitor with thrombin specificity from Rhodnius prolixus. J. Biol. Chem. 268, 16216–16222.PubMedGoogle Scholar
  28. Funk, C., Gmur, J., Herold, R., Straub, P.W., 1971. Reptilase-R: a new reagent in blood coagulation, Br. J. Haematol. 21, 43–52.CrossRefGoogle Scholar
  29. Glenn, J.L., Straight, R., 1978. Mojave rattle snake Crotalus scutulatus scutulatus venom: variation in toxicity with geographical origin. Toxicon 16, 81–84.PubMedCrossRefGoogle Scholar
  30. Gubensek, F., Sket, D., Turk, V., Lebez, D., 1974. Fractionation of Vipera ammodytes venom and seasonal variation of its composition. Toxicon, 12, 167–171.PubMedCrossRefGoogle Scholar
  31. Guimarães-Gomes, V., Oliveira-Carvalho, A.L., Junqueira-de-Azevedo, I.L., Dutra, D.L.S., Pujol-Luz, M., Castro, H.C., Ho, P.L., Zingali, R.B., 2004. Cloning, characterization and structural analysis of a C-type lectin from Bothrops insularis (BiL) venom. Arch. Biochem. Biophys. 432, 1–11.PubMedCrossRefGoogle Scholar
  32. Hjort, P.F., 1957. Intermediate reactions in the coagulation of blood with tissue thromboplastin. Scand. J. Clin. Lab. Invest. 9, 1–183.CrossRefGoogle Scholar
  33. Hofsteenge, J., Taguchi, H., Stone, S.R., 1986. Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors. Biochem. J. 237, 243–251.PubMedGoogle Scholar
  34. Hofsteenge, J., Kieffer, B., Matthies, R., Hemmings, B.A., Stone, S.R., 1988. Amino acid sequence of the ribonuclease inhinbitor from porcine liver reveals the presence of leucine-rich repeats. Biochemistry 27, 8537–8544.PubMedCrossRefGoogle Scholar
  35. Jenny, N.S., Mann, K.G., 1998. Coagulation cascade: an overview, in: Loscalzo, J., Schafer, A.I. (Eds.), Thrombosis and Hemorrhage. Williams and Wilkins, Philadelphia, pp. 3–27.Google Scholar
  36. Jimenez-Porras, J.M., 1964. Intraspecific variations in composition of venom of the jumping viper Bothrops nummifera. Toxicon 2, 187–196.CrossRefGoogle Scholar
  37. Kalafatis, M., Rand, M.D., Mann, K.G., 1994. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J. Biol. Chem. 269, 31869–31880.PubMedGoogle Scholar
  38. Kalafatis, M., Egan, J.O., van’t Veer, C., Cawthern, K.M., Mann, K.G., 1997. The regulation of clotting factors. Crit. Rev. Eukaryotic Gene Expression 7, 241–280.CrossRefGoogle Scholar
  39. Kamiguti, A.S., 2005. Platelets as targets of snake venom metalloproteinases. Toxicon 45, 1041–1049.PubMedCrossRefGoogle Scholar
  40. Kawasaki, T., Fujimura, Y., Usami, Y., Suzuki, M., Miura, S., Sakurai, Y., Makita, K., Taniuchi, Y., Hirano, K., Titani, K., 1996. Complete amino acid sequence and identification of the platelet glycoprotein Ib-binding site of jararaca GPIb-BP, a snake venom protein isolated from Bothrops jararaca. J. Biol. Chem. 271, 10635–10639.PubMedCrossRefGoogle Scholar
  41. Kerns, R.T., Kini, R.M., Stefansson, S., Evans, H.J., 1999. Targeting of venom phospholipases: the strong anticoagulant phospholipase A2 from Naja nigricollis venom binds to coagulation factor Xa to inhibit the prothrombinase complex. Arch. Biochem. Biophys. 369, 107–113.PubMedCrossRefGoogle Scholar
  42. Kirby, E.P., Niewiarowski, S., Stocker, K., Kettner, C., Shaw, E., Brudzynski, T.M. 1979. Thrombocytin, a serine protease from Bothrops atrox venom. 1. Purification and characterization of the enzyme. Biochemistry 18, 3564–3570.PubMedCrossRefGoogle Scholar
  43. Koh, Y., Chung, K., Kim, D., 2000. Purification and cDNA cloning of salmorin that inhibits fibrinogen clotting. Thromb. Res. 99, 389–398.PubMedCrossRefGoogle Scholar
  44. Koo, B.H., Sohn, Y.D., Hwang, K.C., Jang, Y., Kim, D.S., Chung, K.H., 2002. Characterization and cDNA cloning of halyxin, a heterogeneous three-chain anticoagulant protein from the venom of Agkistrodon halys brevicaudus. Toxicon 40, 947–957.PubMedCrossRefGoogle Scholar
  45. Lee, W.H., Zhang, Y., 2003. Molecular cloning and characterization of a platelet glycoprotein Ib-binding protein from the venom of Trimeresurus stejnegeri. Toxicon 41, 885–892.PubMedCrossRefGoogle Scholar
  46. Liu, L.W., Vu, T.K.H., Esmon, C.T., Coughlin, S.R., 1991. The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity. J. Biol. Chem. 266, 16977–16980.PubMedGoogle Scholar
  47. Magro, A.J., Da Silva, R.J., Ramos, P.R.R., Cherubini, M.R., Hatayde, M.R., 2001. Intraspecific variation in the venom electrophoretic profile of recently captured Crotalus durissus terrificus (Lurenti, 1768) snakes. J. Venom. Anim. Toxins 7, 276–301.CrossRefGoogle Scholar
  48. Mann, K.G., 1999. Biochemistry and physiology of blood coagulation. Thromb. Haemost. 82, 165–174.PubMedGoogle Scholar
  49. Mann, K.G., Butenas, S., Brummel, K., 2003. The dynamics of thrombin formation. Arterioscler. Thromb. Vasc. Biol. 23, 17–25.PubMedCrossRefGoogle Scholar
  50. Maraganore, J.M., Bourdon, P., Jablonski, J., Ramachandran, K.L., Fenton, J.W., 2nd, 1990. Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry 29, 7095–7101.PubMedCrossRefGoogle Scholar
  51. Markland, F.S., 1998 Snake venoms and the haemostatic system. Toxicon 36, 1749–1800.PubMedCrossRefGoogle Scholar
  52. Marsh, N., Glatston, A., 1974. Some observations on the venom of the rhinoceros horned viper Bitis nasicornis (Shaw). Toxicon 12, 621–628.PubMedCrossRefGoogle Scholar
  53. Marsh, N.A., 1994. Snake venoms affecting the haemostatic mechanism – a consideration of their mechanisms, practical applications and biological significance. Blood Coagul. Fibrinol. 5, 399–410.Google Scholar
  54. Matsuda, M., Saeki, E., Kasamatsu, A., Nakamikawa, C., Manabe, S., Samejima, Y., 1985. Fibrinogen Kawaguchi: an abnormal fibrinogencharacterized by defective release of fibrinopeptide A. Thromb. Res. 37, 379–390.PubMedCrossRefGoogle Scholar
  55. Matsui, T., Fujimura, Y., Titani, K., 2000. Snake venom proteases affecting hemostasis and thrombosis. Biochim. Biophys. Acta 1477, 146–156.PubMedCrossRefGoogle Scholar
  56. Monteiro, R.Q., Carlini, C.R., Guimarães, J.A., Zingali, R.B., 1997. Distinct bothojaracin isoforms produced by individual jararaca (Bothrops jararaca) snakes. Toxicon 35, 649–657.PubMedCrossRefGoogle Scholar
  57. Monteiro, R.Q., Dutra, D.L.S., Machado, O.L.T., Carlini, C.R., Guimarães, J.A, Bon, C., Zingali, R.B., 1998. Bothrops jararaca snakes produce several bothrojaracin isoforms following an individual pattern. Comp. Biochem. Physiol. B. 120, 791–798.PubMedCrossRefGoogle Scholar
  58. Monteiro, R.Q., Raposo, J.G., Wisner,A., Guimarães, J.A., Bon, C., Zingali, R.B., 1999. Allosteric changes of thrombin catalytic site induced by interaction of bothrojaracin with anion-binding exosities I and II. Biochem. Biophys. Res.Comm. 262, 819–822.PubMedCrossRefGoogle Scholar
  59. Monteiro, R.Q., Zingali, R.B., 2000. Inhibition of prothrombin activation by bothrojaracin, a C-type lectin from Bothrops jararaca venom. Arch. Biochem. Biophys. 382, 123–128.PubMedCrossRefGoogle Scholar
  60. Monteiro, R.B., Bock, P.E., Bianconi, M.L., Zingali, R.B., 2001. Characterization of bothrojaracin interaction with human prothrombin. Protein Science 10, 1897–1904.PubMedCrossRefGoogle Scholar
  61. Monteiro, R.Q., Zingali, R.B., 2002. Bothrojaracin, a proexosite I ligand, inhibits factor Va-accelerated prothrombin activation. Thromb. Haemost. 87, 288–293.PubMedGoogle Scholar
  62. Monteiro, R.Q., Foguel, D., Castro, H.C., Zingali, R.B., 2003. Subunit dissociation, unfolding, and inactivation of bothrojaracin, a C-type lectin-like protein from snake venom. Biochemistry 42, 509–515.PubMedCrossRefGoogle Scholar
  63. Morita, T., 2004. C-type lectin-related proteins from snake venoms. Drug Targets Cardiovasc. Haematol. Disord. 4, 357–373.CrossRefGoogle Scholar
  64. Mounier, C.M., Bon, C., Kini, R.M., 2001. Anticoagulant venom and mammalian secreted phospholipase A2: protein versus phospholipid dependent mechanism of action. Haemostasis 31, 279–287.PubMedGoogle Scholar
  65. Myles, T, Yun, T.H., Hall, S.W., Leung, L.L.K., 2001. An extensive interaction interface between thrombin and factor V is required for factor V activation. J. Biol. Chem. 276, 25143–25149.PubMedCrossRefGoogle Scholar
  66. Murakami, M.T., Arni, R.K., 2005. Thrombomodulin-independent activation of protein C and specificity of hemostatically active snake venom serine proteinases: crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator. J. Biol. Chem. 280, 39309–39315.PubMedCrossRefGoogle Scholar
  67. Nienaber, J., Gaspar, A.R.M., Neitz, A.W., 1999. Savignin, a potent thrombin inhibitor isolated from the salivary glands of the tick Ornithodoros savignyi (Acari: Argasidae). Exp. Parasitol. 20, 583–598.Google Scholar
  68. Oliveira-Carvalho, A.L., Guimarães, P.R., Abreu, P.A., Dutra, D.L., Junqueira-de-Azevedo, I.L., Rodrigues, C.R., Ho, P.L., Castro, H.C., Zingali, R.B., 2008. Identification and characterization of a new member of snake venom thrombin inhibitors from Bothrops insularis using a proteomic approach. Toxicon 51, 659–671.PubMedCrossRefGoogle Scholar
  69. Peng, M., Lu, W., Kirby, E.P., 1991. Alboaggregin-B: a new platelet agonist that binds to platelet membrane glycoprotein Ib. Biochemistry 30, 11529–11536.PubMedCrossRefGoogle Scholar
  70. Peng, M., Holt, J.C., Niewiarowski, S., 1994. Isolation, characterization and amino acid sequence of echicetin b subunit, a specific inhibitor of von Willebrand factor and thrombin interaction with glycoprotein Ib. Biochem. Biophys. Res. Commun. 205, 68–72.PubMedCrossRefGoogle Scholar
  71. Rosing, J., Govers-Riemslag, J.W.P., Yukelson, L., Tans, G., 2001. Factor V activation and inactivation by venom proteases. Hemostasis 31, 241–246.Google Scholar
  72. Salzet, M., Chopin, V., Baerti, J., Matias, I., Malecha, J., 2000. Theromin, a novel leech thrombin inhibitor. J. Biol. Chem. 275, 30774–30780.PubMedCrossRefGoogle Scholar
  73. Santos, A.B.F., 2000. Interaction of viper venom serine peptidases with thrombin receptors on human platelets. FEBS Lett. 477, 199–202.PubMedCrossRefGoogle Scholar
  74. Sekiya, F., Atoda, H., Morita, T., 1993. Isolation and characterization of an anticoagulant protein homologous to botrocetin from the venom of Bothrops jararaca. Biochemistry 32, 6892–6897.PubMedCrossRefGoogle Scholar
  75. Sheehan, J.P., Wu, Q., Tollefsen, D.M., Sadler, J.E., 1993. Mutagenesis selectively modulates inhibition by serpins heparin cofactor II and antithrombin III. Interaction with the anion-binding exosite determines heparin cofactor II specificity. J. Biol. Chem. 268, 3639–3645.PubMedGoogle Scholar
  76. Shiau, S.Y., Ouyang, C., 1965. Isolation of coagulant and anticoagulant principles from the venom of Trimeresurus gramineus. Toxicon 69, 213–220.PubMedCrossRefGoogle Scholar
  77. Solorzano, A., Romero, M., Gutiérrez, J.M., Sasa, M., 1999. Venom composition and diet of the cantil Agkistrodon bilineatus howardgloydi (Serpentes: Viperidae). Southwest. Nat. 44, 478–483.CrossRefGoogle Scholar
  78. Stefano, G.B., Scharrer, B., Smith, E.M., Hughes, T.K., Magazine, H.I., Bilfinger, T.V., Hartman, A.R., Fricchione, G.L., Liu, Y., Makman, M.H., 1996. Opioid and opiate immunoregulatory processes. Crit. Rev. Immunol. 16, 109–144.PubMedCrossRefGoogle Scholar
  79. Stone, S.R., Hofsteenge, J., 1986. Kinetics of the inhibition of thrombin by hirudin. Biochemistry 25, 4622–4628.PubMedCrossRefGoogle Scholar
  80. Stone, S.R., Brown-Luedi, M.L., Rovelli, G., Guidolin, A., McGlynn, E., Monard, D., 1994. Localization of the heparin-binding site of glia-derived nexin/protease nexin 1 by site-directed mutagenesis. Biochemistry 33, 7731–7735.PubMedCrossRefGoogle Scholar
  81. Strube, K.H., Kroger, B., Biolojan, S., Otte, M., Dodt, J., 1993. Isolation, sequence analysis, and cloning of haemadin. An anticoagulant peptide from the Indian leech. J. Biol. Chem. 268, 8590–8595.PubMedGoogle Scholar
  82. Tani, A., Ogawa, T., Nose, T., Nikandrov, N.N., Deshimaru, M., Chijiwa, T., Chang, C.C., Fukumaki, Y., Ohno, M., 2002. Characterization, primary structure and molecular evolution of anticoagulant protein from Agkistrodon acutus venom. Toxicon 40, 803–813.PubMedCrossRefGoogle Scholar
  83. Taniuchi, Y., Kawasaki, T., Fujimura, Y., Suzuki, M., Titani, K., Sakai, Y., Kaku, S., Hisamichi, N., Satoh, N., Takenaka, T., Handa, M., Sawai, Y., 1995. Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress. Biochim. Biophys. Acta 1244, 331–338.PubMedCrossRefGoogle Scholar
  84. Usami, Y., Fujimura, Y., Suzuki, M., Ozeki, Y., Nishio, K., Fukui, H., Titani, K., 1993. Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca. Proc. Natl. Acad. Sci. U.S.A. 90, 928–932.PubMedCrossRefGoogle Scholar
  85. Van de Locht, A, Stubbs, M., Bode, W., Friedrich, T., Bol-Ilschweiler, C., Höffken, W, Huber, R., 1996. The ornithodorin-thrombin crystal structure, a key to the TAP enigma? EMBO J. 15, 6011–6017.PubMedGoogle Scholar
  86. Verstraete, M., Zoldhelyi, P., 1995. Novel antithrombotic drugs in development. Drugs 49, 856–884.PubMedCrossRefGoogle Scholar
  87. Xu, Q., Wu, X.F., Xia, Q.C., Wang, K.Y., 1999. Cloning of a galactose-binding lectin from the venom of Trimeresurus stejnegeri. Biochem. J. 341, 733–737.PubMedCrossRefGoogle Scholar
  88. Xu, X., Liu, Q., Xie, Y., Wu, S.D., 2000. Purification and characterization of anticoagulation factors from the venom of Agkistrodon acutus. Toxicon 38, 1517–1528.PubMedCrossRefGoogle Scholar
  89. Weinger, R.S., Rudy, C., Moake, J.L., Olson, J.D., Cimo, P.L., 1980. Prothrombin Houston: a dysprothrombin identifiable by crossed immunoelectrofocusing and abnormal Echis carinatus venom activation. Blood 55, 811–816.PubMedGoogle Scholar
  90. Wang, W.J., Huang, T.F., 2001. A novel tetrameric venom protein, agglucetin, from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb. Haemost. 86, 1077–1086.PubMedGoogle Scholar
  91. Yeh, C.H., Peng, H.C., Yang, R.S., Huang, T.F., 2001. Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic fibroblast growth factor and suppresses tumor growth by a selective αvβ3 blockade of endothelial cells. Mol. Pharmacol. 59, 1333–1342.PubMedGoogle Scholar
  92. Zang, J., Teng, M., Niu, L., 2003. Purification, crystallization and preliminary crystallographic analysis of AHP IX-bp, a zinc ion and pH-dependent coagulation factor IX binding protein from Agkistrodon halys pallas venom. Acta Crystallogr. D. Biol. Crystallogr. 59, 730–733.PubMedCrossRefGoogle Scholar
  93. Zhang, Y., Wisner, A., Maroun, R.C., Choumet, V., Xiong, Y., Bon, C., 1997. Trimeresurus stejnegeri snake venom plasminogen activator. Site directed mutagenesis and molecular modeling. J. Biol. Chem. 272, 20531–20537.PubMedCrossRefGoogle Scholar
  94. Zingali, R.B., Jandrot-Perrus, M., Guillin, M.C., Bon, C., 1993. Bothrojaracin, a new thrombin inhibitor isolated from Bothrops jararaca venom: characterization and mechanism of thrombin inhibition. Biochemistry 32, 10794–10802.PubMedCrossRefGoogle Scholar
  95. Zingali, R.B., Bianconi, M.L., Monteiro, R.Q., 2001. Interaction of bothrojaracin with prothrombin. Haemostasis 31, 273–278.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Russolina B. Zingali
    • 1
    Email author
  • Ana Cristina Ferraz Nogueira
    • 1
  1. 1.Instituto de Bioquímica Medica, Centro de Ciências da Saúde, UFRJRio de JaneiroBrazil

Personalised recommendations