Strategies for development of novel antithrombotics: Modulating thrombin's procoagulant and anticoagulant properties

Cellular and Molecular Life Sciences

Volumn 53, Issue 9, 1997, Pages 731-736

  Hall, S W ^a   Gibbs, C S ^b   Leung, L L K ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b GILEAD SCIENCES   (United States)

Author keywords

Allosteric; Mutagenesis; Protein C; Structure; Thrombin

Indexed keywords

ACTIVATED PROTEIN C; ANTICOAGULANT AGENT; ANTITHROMBIN III; PROCOAGULANT; SERINE PROTEINASE; SODIUM ION; SYNTHETIC PEPTIDE; THROMBIN; THROMBOMODULIN;

ALLOSTERISM; ANTICOAGULATION; BLOOD CLOTTING; DRUG DESIGN; ENZYME REGULATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; GENETIC ENGINEERING; HUMAN; PROTEIN PROTEIN INTERACTION; REVIEW; SITE DIRECTED MUTAGENESIS;

ALLOSTERIC REGULATION; ANIMALS; ANTICOAGULANTS; ANTITHROMBIN III; ANTITHROMBINS; FIBRINOLYTIC AGENTS; HUMANS; PROTEIN CONFORMATION; PROTEIN ENGINEERING; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBIN; THROMBOMODULIN;

EID: 0030681373     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s000180050092     Document Type: Review

References (36)

1. Fenton J. W. (1995) Thrombin functions and antithrombotic intervention. Thromb. Haemost. 74: 493-498
2. Mann K. G. (1994) Prothrombin and thrombin. In: Hemostasis and Thrombosis, 3rd edition, pp. 184-199. Coleman R. W., Hirsh J., Marder V. J. and Salzman E. W. (eds), Lippincott, Philadelphia
3. Bajzar L., Mavel R. and Nesheim M. E. (1995) Purification and characterization of TAF1, a thrombin-activatable fibrinolysis inhibitor. J. Biol. Chem. 270: 1447-1452
4. Esmon C. T. (1995) Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface. FASEB J. 9: 946-955
5. Bode W., Mayr I., Baumann U., Huber R., Stone S. R. and Hofsteenge J. (1989) The refined 1.9 A crystal structure of human α-thrombin: interaction with D-Phe-Pro-Arg-chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 8: 3467-3475
6. Grütter M. G., Priestle J. P., Rahuel J., Grossenbacher H., Bode W., Hofsteenge J. et al. (1990) Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibitor. EMBO J. 9: 2361-2365
7. Rydel T. J., Ravichandran K. G., Tulinsky A., Bode W., Huber R., Roitsch C. et al. (1990) The structure of a complex of recombinant hirudin and human alpha-thrombin. Science 249: 277-280
8. Xue J., Wu Q., Westfield L. A., Tuley K. A., Lu D., Zhang Q. et al. (1996) A genetically engineered mouse model of total prothrombin deficiency. Blood 88, Suppl 1: 468a
9. Fenton II J. W., Olson T. A., Zabinski M. P. and Wilner G. D. (1988) Anion-binding exosite of human α-thrombin and fibrin(ogen) recognition. Biochemistry 27: 7106-7112
10. Stone S. R. and Hofsteenge J. (1986) Kinetics of the inhibition of thrombin by hirudin. Biochemistry 25: 4622-4628
11. Sheehan J. P., Wu Q., Tollefsen D. M. and Sadler J. E. (1993) Mutagenesis of thrombin 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
12. Liu L. W., Vu T. K. H, Esmon C. T. and 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
13. Li W. X., Kaplan A. V., Grant G. W., Toole J. J. and Leung E. E. K. (1994) A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation. Blood 83: 677-682
14. Sheehan J. P. and Sadler J. F. (1994) Molecular mapping of the heparin-binding exosite of thrombin. Proc. Natl Acad. Sci. USA 91: 5518-5522
15. Gan Z. R., Li Y., Chen Z., Lewis S. D. and Shafer J. A. (1994) Identification of basic amino acid residues in thrombin essential for heparin-catalyzed inactivation by antithrombin III. J. Biol. Chem. 269: 1301-1305
16. Arni R. K., Padmanabhan K., Padmanabhan K. P., Wu T. P. and Tulinsky A. (1993) Structure of the noncovalent complexes of human and bovine prothrombin fragment 2 with human PPACK-thrombin. Biochemistry 32: 4727-4737
17. Esmon C. T. and 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
18. Tsiang M., Jain A. K., Dunn K. E., Rojas M. E., Leung L. L. K. and Gibbs C. S. (1995) Functional mapping of the surface residues of thrombin. J. Biol. Chem. 270: 16854-16863
19. van de Locht A., Stubbs M. T., Bauer M. and Bode W. (1996) Crystallographic evidence that the F2 kringle catalytic domain linker of prothrombin does not cover the fibrinogen recognition exosite. J. Biol. Chem. 271: 3413-3416
20. LeBonniec B. F. and Esmon C. T. (1991) Glu-192 [to] Gln substitution in thrombin mimics the catalytic switch induced by thrombomodulin. Proc. Natl Acad. Sci. USA 88: 7371-7375
21. Vindigni A., White C. E., Komines E. A. and Di Cera E. (1997) Energetics of thrombin-thrombomodulin interaction. Biochemistry 36: 6674-6681
22. +-activated enzyme. Biochemistry 31: 11721-11730
23. De Cristofaro R. and Di Cera E. (1992) Modulation of thrombin-fibrinogen interaction by specific ion effects. Biochemistry 31: 257-265
24. Dang Q. D., Vindigni A. and Di Cera E. (1995) An allosteric switch controls the procoagulant and anticoagulant activities of thrombin. Proc. Natl Acad. Sci. USA 92: 5977-5981
25. Ayala Y. M., Vindigni A., Nayal M., Spolar R. S., Record M. T. and Di Cera E. (1995) Thermodynamic investigation of hirudin binding to the slow and fast forms of thrombin: evidence for folding transitions in the inhibitor and protease coupled to binding. J. Molec. Biol. 253: 787-798
26. + binding site of thrombin. J. Biol. Chem. 270: 22089-22092
27. Dang Q. D., Guinto E. R. and Di Cera F. (1997) Rational engineering of activity and specificity in a serine protease. Nature Biotechnology 15: 146-149
28. +-induced allosteric regulation of catalytic activity in serine proteases. Proc. Natl Acad. Sci. USA 93: 10653-10656
29. Guinto E. R., Vindigni A., Ayala Y. M., Dang Q. D. and Di Cera E. (1995) Identification of residues linked to the slow-fast transition of thrombin. Proc. Natl Acad. Sci. USA 92: 11185-11189
30. Wu Q., Sheehan J. P., Tsiang M., Lentz S. R., Birktoft J. J. and Sadler J. E. (1991) Single amino acid substitutions dissociate fibrinogen-clotting and thrombomodulin-binding activities of human thrombin. Proc. Natl Acad. Sci. USA 88: 6775-6779
31. Gibbs C. S., Coutre S. E., Tsiang M., Li W. X., Jain A. K., Dunn K. E. et al. (1995) Conversion of thrombin into an anticoagulant by protein engineering. Nature 378: 413-416
32. Tsiang M., Paborsky L. R., Li W. X., Jain A. K., Mao C. T. et al. (1996) Protein engineering thrombin for optimal specificity and potency of anticoagulant activity in vivo. Biochemistry 35: 16449-16457
33. Hanson S., Harker L., Kelly A., Fernandez J., Griffin J. and Gibbs C. S. (1997) Antithrombotic effects of selective activation of endogenous protein C. Thromb Haemost (June) Suppl: 419
34. Berg D. T., Wiley M. R. and Grinnell B. W. (1996) Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator. Science 273: 1389-1391
35. Rezaie A. R. (1996) Tryptophan 60-D in the B-insertion loop of thrombin modulates the thrombin-antithrombin reaction. Biochemistry 35: 1918-1924
36. Tsiang M., Jain A. K. and Gibbs C. S. (1997) Functional requirements for inhibition of thrombin by antithrombin III in the presence and absence of heparin. J. Biol. Chem. 272: 12024-12029