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Table of Contents
Vol. 31, No. 3-6, 2001
Issue release date: May–December 2001 (March 2002)
Section title: Fibrinolysis
Haemostasis 2001;31:133–140
(DOI:10.1159/000048056)

Snake Venom Proteinases as Tools in Hemostasis Studies: Structure-Function Relationship of a Plasminogen Activator Purified from Trimeresurus stejnegeri Venom

Wisner A. · Braud S. · Bon C.
Unité des Venins, Institut Pasteur, Paris, France
email Corresponding Author

Abstract

Snake venom serine proteinases affect many steps of the blood coagulation cascade. Each of them usually acts selectively on one coagulation factor. They are therefore potentially useful components to study the mechanisms of action, the regulation and the structure-function relationships of human serine proteinase coagulation factors. This strategy is illustrated for a plasminogen activator purified from Trimeresurus stejnegeri venom.

© 2002 S. Karger AG, Basel


  

Key Words

  • Snake venom
  • Proteinase
  • Plasminogen activator
  • Structure-function
  • Haemostasis

References

  1. Siezen RJ: Multi-domain, cell-envelope proteinases of lactic acid bacteria. Antonie Van Leeuwenhoek 1999;76:139–155.

    External Resources

  2. Rudenskaya GN, Bogdanova EA, Revina LP, Golovkin BN, Stepanov VM: Macluralisin – a serine proteinase from fruits of Maclura pomifera (Raf.). Schneid Planta 1995;196:174–179.
  3. Neurath H: Evolution of proteolytic enzymes. Science 1984;224:350–357.

    External Resources

  4. Neurath H: Proteolytic enzymes, past and present. Fed Proc 1985;44:2907–2913.

    External Resources

  5. DiBella EE, Scheraga HA: Thrombin specificity: Further evidence for the importance of the beta-insertion loop and Trp96. Implications of the hydrophobic interaction between Trp96 and Pro60B Pro60C for the activity of thrombin. J Protein Chem 1998;17:197–208.
  6. Hedstrom L, Szilagyi L, Rutter WJ: Converting trypsin to chymotrypsin: The role of surface loops. Science 1992;255:1249–1253.

    External Resources

  7. Le Bonniec BF, Guinto ER, MacGillivray RT, Stone SR, Esmon CT: The role of thrombin’s Tyr-Pro-Pro-Trp motif in the interaction with fibrinogen, thrombomodulin, protein C, antithrombin III, and the Kunitz inhibitors. J Biol Chem 1993;268:19055–19061.
  8. Madison EL, Goldsmith EJ, Gerard RD, Gething MJ, Sambrook JF: Serpin-resistant mutants of human tissue-type plasminogen activator. Nature 1989;339:721–724.
  9. Matthews BW, Sigler PB, Henderson R, Blow DM: Three-dimensional structure of tosyl-alpha-chymotrypsin. Nature 1967;214:652–656.

    External Resources

  10. Ruhlmann A, Kukla D, Schwager P, Bartels K, Huber R: Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. Crystal structure determination and stereochemistry of the contact region. J Mol Biol 1973;77:417–436.

    External Resources

  11. Bode W, Chen Z: The X-ray structures of porcine pancreatic kallikrein and of its complex with bovine pancreatic trypsin inhibitor. Adv Exp Med Biol 1983;156:289–308.

    External Resources

  12. Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J: The refined 1.9 Å crystal structure of human alpha-thrombin: Interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 1989;8:3467–3475.
  13. Padmanabhan K, Padmanabhan KP, Tulinsky A, Park CH, Bode W, Huber R, Blankenship DT, Cardin AD, Kisiel W: Structure of human des(1–45) factor Xa at 2.2 Å resolution. J Mol Biol 1993;232:947–966.
  14. Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W: The 2.3 angstrom crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator. J Mol Biol 1996:258:117–135.
  15. Greer J: Comparative modeling methods: Application to the family of the mammalian serine proteases. Proteins 1990;7:317–334.

    External Resources

  16. Perona JJ, Craik CS: Structural basis of substrate specificity in the serine proteases (Review). Protein Sci 1995:4:337–360.
  17. Perona JJ, Craik CS: Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold. J Biol Chem 1997;272:29987–29990.
  18. Kini RM, Evans HJ: Effects of snake venom proteins on blood platelets. Toxicon 1990;28:1387–1422.
  19. Markland FS Jr: Snake venoms. Drugs 1997;3:1–10.
  20. Mitrakul C: Effect of five Thai snake venoms on coagulation, fibrinolysis and platelet aggregation. Southeast Asian J Trop Med Public Health 1979;10:266–275.
  21. Marrakchi N, Zingali RB, Karoui H, Bon C, el Ayeb M: Cerastocytin, a new thrombin-like platelet activator from the venom of the Tunisian viper Cerastes cerastes. Biochim Biophys Acta 1995;1244:147–156.
  22. Serrano SM, Mentele R, Sampaio CA, Fink E: Purification, characterization, and amino acid sequence of a serine proteinase, PA-BJ, with platelet-aggregating activity from the venom of Bothrops jararaca. Biochemistry 1995;34:7186–7193.

    External Resources

  23. Kirby EP, Niewiarowski S, Stocker K, Kettner C, Shaw E, Brudzynski TM: Thrombocytin, a serine protease from Bothrops atrox venom. 1. Purification and characterization of the enzyme. Biochemistry 1979;18:3564–3570.

    External Resources

  24. Santos ABF, Serrano SMT, Kuliopulos A, Niewiarouski S: Interaction of viper venom serine peptidases with thrombin receptors on human platelets. FEBS Lett 2000;477:199–202.
  25. Kisiel W: Molecular properties of the factor V-activating enzyme from Russell’s viper venom. J Biol Chem 1979;254:12230–12234.

    External Resources

  26. Stocker K, Fischer H, Meier J, Brogli M, Svendsen L: Characterization of the protein C activator Protac from the venom of the southern copperhead (Agkistrodon contortrix) snake. Toxicon 1987;25:239–252.
  27. Pirkle H, Theodor I: Thrombin-like venom enzymes: Structure and function. Adv Exp Med Biol 1990;281:165–175.
  28. Pirkle H: Thrombin-like enzymes from snake venoms: An updated inventory. Scientific and Standardization Committee’s Registry of Exogenous Hemostatic Factors. Thromb Haemost 1998:79:675–683.
  29. Stocker K, Fischer H, Meier J: Thrombin-like snake venom proteinases. Toxicon 1982;20:265–273.
  30. Zhang Y, Wisner A, Xiong Y, Bon C: A novel plasminogen activator from snake venom. Purification, characterization, and molecular cloning. J Biol Chem 1995;270:10246–10255.
  31. Parry MA, Jacob U, Huber R, Wisner A, Bon C, Bode W: The crystal structure of the novel snake venom plasminogen activator TSV-PA: A prototype structure for snake venom serine proteinases. Structure 1998;6:1195–1206.
  32. Nakashima K, Ogawa T, Oda N, Hattori M, Sakaki Y, Kihara H, Ohno M: Accelerated evolution of Trimeresurus flavoviridis venom gland phospholipase A2 isozymes. Proc Natl Acad Sci USA 1993;90:5964–5968.
  33. Nakashima K, Nobuhisa I, Deshimaru M, Nakai M, Ogawa T, Shimohigashi Y, Fukumaki Y, Hattori M, Sakaki Y, Hattori S: Accelerated evolution in the protein-coding regions is universal in Crotalinae snake venom gland phospholipase A2 isozyme genes. Proc Natl Acad Sci USA 1995;92:5605–5609.

    External Resources

  34. Ogawa T, Oda N, Nakashima K, Sasaki H, Hattori M, Sakaki Y, Kihara H, Ohno M: Unusually high conservation of untranslated sequences in cDNAs for Trimeresurus flavoviridis phospholipase A2 isozymes. Proc Natl Acad Sci USA 1992;89:8557–8561.

    External Resources

  35. Collen D: On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemost 1980;43:77–89.

    External Resources

  36. Collen D, Lijnen HR, Todd PA, Goa KL: Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent. Drugs 1989;38:346–388.
  37. Collen D, Lijnen HR: Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991;78:3114–3124.
  38. Lijnen HR, Collen D: Molecular interactions between tissue-type plasminogen activator and plasminogen. Methods Enzymol 1993;223:197–206.
  39. Kohnert U, Hellerbrand K, Martin U, Stern A, Popp F, Fischer S: The recombinant Escherichia coli-derived protease-domain of tissue-type plasminogen activator is a potent and fibrin specific fibrinolytic agent. Fibrinolysis 1996;10:93–102.
  40. Martin U, Kohnert U, Stern A, Popp F, Fischer S: Comparison of the recombinant Escherichia coli-produced protease domain of tissue-type plasminogen activator with alteplase, reteplase and streptokinase in a canine model of coronary artery thrombolysis. Thromb Haemost 1996;76:1096–1101.
  41. Zhang Y, Wisner A, Maroun RC, Choumet V, Xiong Y, Bon C: Trimeresurus stejnegeri snake venom plasminogen activator. Site-directed mutagenesis and molecular modeling. J Biol Chem 1997;272:20531–20537.
  42. Shohet RV, Spitzer S, Madison EL, Bassel-Duby R, Gething MJ, Sambrook JF: Inhibitor-resistant tissue-type plasminogen activator: An improved thrombolytic agent in vitro. Thromb Haemost 1994;71:124–128.
  43. Itoh N, Tanaka N, Mihashi S, Yamashina I: Molecular cloning and sequence analysis of cDNA for batroxobin, a thrombin-like snake venom enzyme. J Biol Chem 1987;262:3132–3135.
  44. Au LC, Lin SB, Chou JS, Teh GW, Chang KJ, Shih CM: Molecular cloning and sequence analysis of the cDNA for ancrod, a thrombin-like enzyme from the venom of Calloselasma rhodostoma. Biochem J 1993;294(pt 2):387–390.
  45. Tokunaga F, Nagasawa K, Tamura S, Miyata T, Iwanaga S, Kisiel W: The factor V-activating enzyme (RVV-V) from Russell’s viper venom. Identification of isoproteins RVV-V alpha, -V beta, and -V gamma and their complete amino acid sequences. J Biol Chem 1988;263:17471–17481.
  46. Wang D, Bode W, Huber R: Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 Å resolution. J Mol Biol 1985;185:595–624.

  

Author Contacts

Dr. Cassian Bon
Head of the Venoms Unit, Institut Pasteur
25–28, rue du Docteur-Roux
F–75724 Paris Cedex 15 (France)
Tel. +33 1 45 68 86 85, Fax +33 1 40 61 30 57, E-Mail cbon@pasteur.fr

  

Article Information

Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 0, Number of References : 46

  

Publication Details

Haemostasis (International Journal on Haemostasis and Thrombosis Research)
Official Journal of the ‘Mediterranean League against Thromboembolic Diseases’

Vol. 31, No. 3-6, Year 2001 (Cover Date: May-December 2001 (Released March 2002))

Journal Editor: H.C. Hemker, Maastricht; V.V. Kakkar, London
ISSN: 0301–0147 (print), 1423–0038 (Online)

For additional information: http://www.karger.com/journals/hae


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Snake venom serine proteinases affect many steps of the blood coagulation cascade. Each of them usually acts selectively on one coagulation factor. They are therefore potentially useful components to study the mechanisms of action, the regulation and the structure-function relationships of human serine proteinase coagulation factors. This strategy is illustrated for a plasminogen activator purified from Trimeresurus stejnegeri venom.

© 2002 S. Karger AG, Basel


  

Author Contacts

Dr. Cassian Bon
Head of the Venoms Unit, Institut Pasteur
25–28, rue du Docteur-Roux
F–75724 Paris Cedex 15 (France)
Tel. +33 1 45 68 86 85, Fax +33 1 40 61 30 57, E-Mail cbon@pasteur.fr

  

Article Information

Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 0, Number of References : 46

  

Publication Details

Haemostasis (International Journal on Haemostasis and Thrombosis Research)
Official Journal of the ‘Mediterranean League against Thromboembolic Diseases’

Vol. 31, No. 3-6, Year 2001 (Cover Date: May-December 2001 (Released March 2002))

Journal Editor: H.C. Hemker, Maastricht; V.V. Kakkar, London
ISSN: 0301–0147 (print), 1423–0038 (Online)

For additional information: http://www.karger.com/journals/hae


Article / Publication Details

First-Page Preview
Abstract of Fibrinolysis

Published online: 3/25/2002
Issue release date: May–December 2001 (March 2002)

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 0

ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)

For additional information: http://www.karger.com/PHT


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Siezen RJ: Multi-domain, cell-envelope proteinases of lactic acid bacteria. Antonie Van Leeuwenhoek 1999;76:139–155.

    External Resources

  2. Rudenskaya GN, Bogdanova EA, Revina LP, Golovkin BN, Stepanov VM: Macluralisin – a serine proteinase from fruits of Maclura pomifera (Raf.). Schneid Planta 1995;196:174–179.
  3. Neurath H: Evolution of proteolytic enzymes. Science 1984;224:350–357.

    External Resources

  4. Neurath H: Proteolytic enzymes, past and present. Fed Proc 1985;44:2907–2913.

    External Resources

  5. DiBella EE, Scheraga HA: Thrombin specificity: Further evidence for the importance of the beta-insertion loop and Trp96. Implications of the hydrophobic interaction between Trp96 and Pro60B Pro60C for the activity of thrombin. J Protein Chem 1998;17:197–208.
  6. Hedstrom L, Szilagyi L, Rutter WJ: Converting trypsin to chymotrypsin: The role of surface loops. Science 1992;255:1249–1253.

    External Resources

  7. Le Bonniec BF, Guinto ER, MacGillivray RT, Stone SR, Esmon CT: The role of thrombin’s Tyr-Pro-Pro-Trp motif in the interaction with fibrinogen, thrombomodulin, protein C, antithrombin III, and the Kunitz inhibitors. J Biol Chem 1993;268:19055–19061.
  8. Madison EL, Goldsmith EJ, Gerard RD, Gething MJ, Sambrook JF: Serpin-resistant mutants of human tissue-type plasminogen activator. Nature 1989;339:721–724.
  9. Matthews BW, Sigler PB, Henderson R, Blow DM: Three-dimensional structure of tosyl-alpha-chymotrypsin. Nature 1967;214:652–656.

    External Resources

  10. Ruhlmann A, Kukla D, Schwager P, Bartels K, Huber R: Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. Crystal structure determination and stereochemistry of the contact region. J Mol Biol 1973;77:417–436.

    External Resources

  11. Bode W, Chen Z: The X-ray structures of porcine pancreatic kallikrein and of its complex with bovine pancreatic trypsin inhibitor. Adv Exp Med Biol 1983;156:289–308.

    External Resources

  12. Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J: The refined 1.9 Å crystal structure of human alpha-thrombin: Interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 1989;8:3467–3475.
  13. Padmanabhan K, Padmanabhan KP, Tulinsky A, Park CH, Bode W, Huber R, Blankenship DT, Cardin AD, Kisiel W: Structure of human des(1–45) factor Xa at 2.2 Å resolution. J Mol Biol 1993;232:947–966.
  14. Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W: The 2.3 angstrom crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator. J Mol Biol 1996:258:117–135.
  15. Greer J: Comparative modeling methods: Application to the family of the mammalian serine proteases. Proteins 1990;7:317–334.

    External Resources

  16. Perona JJ, Craik CS: Structural basis of substrate specificity in the serine proteases (Review). Protein Sci 1995:4:337–360.
  17. Perona JJ, Craik CS: Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold. J Biol Chem 1997;272:29987–29990.
  18. Kini RM, Evans HJ: Effects of snake venom proteins on blood platelets. Toxicon 1990;28:1387–1422.
  19. Markland FS Jr: Snake venoms. Drugs 1997;3:1–10.
  20. Mitrakul C: Effect of five Thai snake venoms on coagulation, fibrinolysis and platelet aggregation. Southeast Asian J Trop Med Public Health 1979;10:266–275.
  21. Marrakchi N, Zingali RB, Karoui H, Bon C, el Ayeb M: Cerastocytin, a new thrombin-like platelet activator from the venom of the Tunisian viper Cerastes cerastes. Biochim Biophys Acta 1995;1244:147–156.
  22. Serrano SM, Mentele R, Sampaio CA, Fink E: Purification, characterization, and amino acid sequence of a serine proteinase, PA-BJ, with platelet-aggregating activity from the venom of Bothrops jararaca. Biochemistry 1995;34:7186–7193.

    External Resources

  23. Kirby EP, Niewiarowski S, Stocker K, Kettner C, Shaw E, Brudzynski TM: Thrombocytin, a serine protease from Bothrops atrox venom. 1. Purification and characterization of the enzyme. Biochemistry 1979;18:3564–3570.

    External Resources

  24. Santos ABF, Serrano SMT, Kuliopulos A, Niewiarouski S: Interaction of viper venom serine peptidases with thrombin receptors on human platelets. FEBS Lett 2000;477:199–202.
  25. Kisiel W: Molecular properties of the factor V-activating enzyme from Russell’s viper venom. J Biol Chem 1979;254:12230–12234.

    External Resources

  26. Stocker K, Fischer H, Meier J, Brogli M, Svendsen L: Characterization of the protein C activator Protac from the venom of the southern copperhead (Agkistrodon contortrix) snake. Toxicon 1987;25:239–252.
  27. Pirkle H, Theodor I: Thrombin-like venom enzymes: Structure and function. Adv Exp Med Biol 1990;281:165–175.
  28. Pirkle H: Thrombin-like enzymes from snake venoms: An updated inventory. Scientific and Standardization Committee’s Registry of Exogenous Hemostatic Factors. Thromb Haemost 1998:79:675–683.
  29. Stocker K, Fischer H, Meier J: Thrombin-like snake venom proteinases. Toxicon 1982;20:265–273.
  30. Zhang Y, Wisner A, Xiong Y, Bon C: A novel plasminogen activator from snake venom. Purification, characterization, and molecular cloning. J Biol Chem 1995;270:10246–10255.
  31. Parry MA, Jacob U, Huber R, Wisner A, Bon C, Bode W: The crystal structure of the novel snake venom plasminogen activator TSV-PA: A prototype structure for snake venom serine proteinases. Structure 1998;6:1195–1206.
  32. Nakashima K, Ogawa T, Oda N, Hattori M, Sakaki Y, Kihara H, Ohno M: Accelerated evolution of Trimeresurus flavoviridis venom gland phospholipase A2 isozymes. Proc Natl Acad Sci USA 1993;90:5964–5968.
  33. Nakashima K, Nobuhisa I, Deshimaru M, Nakai M, Ogawa T, Shimohigashi Y, Fukumaki Y, Hattori M, Sakaki Y, Hattori S: Accelerated evolution in the protein-coding regions is universal in Crotalinae snake venom gland phospholipase A2 isozyme genes. Proc Natl Acad Sci USA 1995;92:5605–5609.

    External Resources

  34. Ogawa T, Oda N, Nakashima K, Sasaki H, Hattori M, Sakaki Y, Kihara H, Ohno M: Unusually high conservation of untranslated sequences in cDNAs for Trimeresurus flavoviridis phospholipase A2 isozymes. Proc Natl Acad Sci USA 1992;89:8557–8561.

    External Resources

  35. Collen D: On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemost 1980;43:77–89.

    External Resources

  36. Collen D, Lijnen HR, Todd PA, Goa KL: Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent. Drugs 1989;38:346–388.
  37. Collen D, Lijnen HR: Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991;78:3114–3124.
  38. Lijnen HR, Collen D: Molecular interactions between tissue-type plasminogen activator and plasminogen. Methods Enzymol 1993;223:197–206.
  39. Kohnert U, Hellerbrand K, Martin U, Stern A, Popp F, Fischer S: The recombinant Escherichia coli-derived protease-domain of tissue-type plasminogen activator is a potent and fibrin specific fibrinolytic agent. Fibrinolysis 1996;10:93–102.
  40. Martin U, Kohnert U, Stern A, Popp F, Fischer S: Comparison of the recombinant Escherichia coli-produced protease domain of tissue-type plasminogen activator with alteplase, reteplase and streptokinase in a canine model of coronary artery thrombolysis. Thromb Haemost 1996;76:1096–1101.
  41. Zhang Y, Wisner A, Maroun RC, Choumet V, Xiong Y, Bon C: Trimeresurus stejnegeri snake venom plasminogen activator. Site-directed mutagenesis and molecular modeling. J Biol Chem 1997;272:20531–20537.
  42. Shohet RV, Spitzer S, Madison EL, Bassel-Duby R, Gething MJ, Sambrook JF: Inhibitor-resistant tissue-type plasminogen activator: An improved thrombolytic agent in vitro. Thromb Haemost 1994;71:124–128.
  43. Itoh N, Tanaka N, Mihashi S, Yamashina I: Molecular cloning and sequence analysis of cDNA for batroxobin, a thrombin-like snake venom enzyme. J Biol Chem 1987;262:3132–3135.
  44. Au LC, Lin SB, Chou JS, Teh GW, Chang KJ, Shih CM: Molecular cloning and sequence analysis of the cDNA for ancrod, a thrombin-like enzyme from the venom of Calloselasma rhodostoma. Biochem J 1993;294(pt 2):387–390.
  45. Tokunaga F, Nagasawa K, Tamura S, Miyata T, Iwanaga S, Kisiel W: The factor V-activating enzyme (RVV-V) from Russell’s viper venom. Identification of isoproteins RVV-V alpha, -V beta, and -V gamma and their complete amino acid sequences. J Biol Chem 1988;263:17471–17481.
  46. Wang D, Bode W, Huber R: Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 Å resolution. J Mol Biol 1985;185:595–624.