The structure of thrombin, a chameleon-like proteinase

Journal of Thrombosis and Haemostasis

Volumn 3, Issue 11, 2005, Pages 2379-2388

  Bode, Wolfram ^a  

^a MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

Antithrombotics; Coagulation; Crystal structures; Inhibition; Thrombin; Zymogen activation

Indexed keywords

ALDEHYDE; AMIDE; APROTININ; ARGATROBAN; ARGININE DERIVATIVE; BENZAMIDINE DERIVATIVE; HEPARIN; HIRUDIN; ISOCOUMARIN DERIVATIVE; KETONE; PROTEINASE; SERINE PROTEINASE; THROMBIN; TRYPSINOGEN; XIMELAGATRAN;

BLOOD CLOTTING; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG STRUCTURE; HUMAN; MEDICAL RESEARCH; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALS; BLOOD COAGULATION; CRYSTALLIZATION; DRUG DESIGN; HIRUDINS; HUMANS; PEPTIDE HYDROLASES; PROTEIN CONFORMATION; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS; THROMBIN; THROMBOMODULIN;

EID: 28044444092     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2005.01356.x     Document Type: Review

References (101)

1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res 2000; 28: 235-42.
2. Davie EW. A brief historical review of the waterfall/cascade of blood coagulation. J Biol Chem 2003; 278: 50819-32.
3. Hougie C. The waterfall-cascade and autoprothrombin hypotheses of blood coagulation: personal reflections from an observer. J Thromb Haemost 2004; 2: 1225-33.
4. Stubbs MT, Bode W. A player of many parts: the spotlight falls on thrombin's structure. Thromb. Res 1993; 69: 1-58.
5. Stubbs MT, Bode W. Coagulation factors and their inhibitors. Curr Opin Struct Biol 1994; 4: 823-32.
6. Stubbs MT, Bode W. The clot thickens: clues provided by thrombin structure. Trends Biochem Sci 1995; 20: 23-8.
7. Bode W, Brandstetter H, Mather T, Stubbs MT. Comparative analysis of haemostatic proteinases: structural aspects of thrombin, factor Xa, factor IXa and protein C. Thromb Haemost 1997; 78: 501-11.
8. Huber R, Kukla D, Bode W, Schwager P, Bartels K, Deisenhofer J, Steigemann W. Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. J Mol Biol 1974; 89: 73-101.
9. Laskowski M Jr, Kato I. Protein inhibitors of proteinases. Annu Rev Biochem 1980; 49: 593-626.
10. Bode W, Huber R. Natural protein proteinase inhibitors and their interaction with proteinases. Eur J Biochem 1992; 204: 433-51.
11. Bode W, Schwager P. The refined crystal structure of bovine beta-trypsin at 1.8 A resolution. J Mol Biol 1975; 98: 693-717.
12. Bode W, Fehlhammer H, Huber R. Crystal structure of bovine trypsinogen at 1.8 Å resolution. J Mol Biol 1976; 106: 325-35.
13. Bode W, Schwager P, Huber R. The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. The refined crystal structures of the bovine trypsinogen-pancreatic trypsin inhibitor complex and of its ternary complex with Ile-Val at 1.9 Å resolution. J Mol Biol 1978; 118: 99-112.
14. Huber R, Bode W. Structural basis of the activation and action of trypsin. Acc Chem Res 1978; 11: 114-22.
15. Bode W. The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. II. The binding of the pancreatic trypsin inhibitor and of isoleucine-valine and of sequentially related peptides to trypsinogen and to p-guanidinobenzoate-trypsinogen. J Mol Biol 1979; 127: 357-74.
16. Bode W, Huber R. Induction of the bovine trypsinogen-trypsin transition by peptides sequentially similar to the N-terminus of trypsin. FEBS-Let 1976; 68: 231-6.
17. Vu TK, Wheaton VI, Hung DT, Charo I, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature 1991; 353: 674-7.
18. Magnusson S, Peterson TE, Sottrup-Jensen L, Claeys H. Complete primary structure of prothrombin: Isolation, structure and reactivity of ten carboxylated glutamic acid residues and regulation of prothrombin activation by thrombin. In: Reich E, Rifkin DB, Shaw E, eds. Proteases and Biological Control. NY: Cold Spring Harbour, Cold Spring Harbour Lab., 1975: 123-49.
19. Tsernoglou D, Walz DA, McCoy LE, Seegers WH. An x-ray crystallographic study of thrombin. J Biol Chem 1974; 249: 999.
20. McKay DB, Kay LM, Stroud RM. In: Lundblad RL, Fenton JW, Mann KG, eds. Chemistry and Biology of Thrombin. Ann Arbor: Ann Arbor Science Publ., 1977: 113-21.
21. Bode W. Nonenzymatic activation of trypsin-like serine proteinases. Biol Chem Hoppe-Seyler 1985; 366: 767.
22. Wei A., Mayr I, Bode W. The refined 2.3 Å crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor. FEBS Lett 1988; 234: 367-73.
23. 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: 3467-75.
24. Bode W, Turk D, Karshikov A. The refined 1.9-Å X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Protein Sci 1992; 1: 426-7127.
25. Kettner C, Shaw E. D-Phe-Pro-ArgCH2C1-A selective affinity label for thrombin. Thromb Res 1979; 14: 969-73.
26. Kam CM, Fujikawa K, Powers JC. Mechanism-based isocoumarin inhibitors for trypsin and blood coagulation serine proteases: new anticoagulants. Biochemistry 1988; 27: 2547-57.
27. Bajusz S, Barabas E, Tolnay P, Szell E, Bagdy D. Inhibition of thrombin and trypsin by tripeptide aldehydes. Int J Pept Protein Res 1978; 12: 217-21.
28. Kikumoto R, Tamao Y, Tezuka T, Tonomura S, Hara H, Ninomiya K, Hijikata A, Okamoto S. Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[(3- methyl-1,2,3,4-tetrahydro-8-quinolinyl) sulfonyl]-1-arginyl)]-2- piperidinecarboxylic acid. Biochemistry 1984; 23: 85-90.
29. Stürzebecher J, Markwardt F, Voigt B, Wagner G, Walsmann P. Cyclic amides of N-alpha-arylsulfonylaminoacylated 4-amidino-phenylalanine - tight binding inhibitors of thrombin. Thromb Res 1983; 29: 635-42.
30. Bode W, Turk D, Stürzebecher J. Geometry of binding of the benzamidine- and arginine-based inhibitors NAPAP and MQPA to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP-thrombin and MQPA-thrombin. Eur J Biochem 1990; 193: 175-82.
31. Matsuzaki T, Sasaki C, Okumura C, Umeyama H. X-ray analysis of a thrombin inhibitor-trypsin complex. J Biochem (Tokyo) 1989; 105: 949-52.
32. Steinmetzer T, Stürzebecher J. Progress in the development of synthetic thrombin inhibitors as new orally active anticoagulants. Curr Med Chem 2004; 11: 2297-321.
33. Gustafsson D. Oral direct thrombin inhibitors in clinical development. J Intern Med 2003; 254: 322-34.
34. Banner DW, Hadvary P. Crystallographic analysis at 3.0-Å resolution of the binding to human thrombin of four active site-directed inhibitors. J Biol Chem 1991; 266: 20085-93.
35. Brandstetter H, Turk D, Hoeffken HW, Grosse D, Stürzebecher J, Martin PD, Edwards BF, Bode W. Refined 2.3 Å X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics. J Mol Biol 1992; 226: 1085-99.
36. Skrzypczak-Jankun E, Carperos VE, Ravichandran KG, Tulinsky A, Westbrook M, Maraganore JM. Structure of the hirugen and hirulog 1 complexes of alpha-thrombin. J Mol Biol 1991; 221: 1379-93.
37. Löbermann H, Lottspeich F, Bode W, Huber R. Interaction of human alpha 1-proteinase inhibitor with chymotrypsinogen A and crystallization of a proteolytically modified alpha 1-proteinase inhibitor. Hoppe Seylers Z Physiol Chem 1982; 363: 1377-88.
38. Loebermann H, Tokuoka R, Deisenhofer J, Huber R. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J Mol Biol 1984; 177: 531-57.
39. Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C, Fenton JW II. The structure of a complex of recombinant hirudin and human alpha-thrombin. Science 1990; 249: 277-80.
40. Grutter MG, Priestle JP, Rahuel J, Grossenbacher H, Bode W, Hofsteenge J, Stone SR. Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition. EMBO J 1990; 9: 2361-5.
41. Ascenzi P, Amiconi G, Bode W, Bolognesi M, Coletta M, Menegatti E. Proteinase inhibitors from the European medicinal leech Hirudo medicinalis: structural, functional and biomedical aspects. Mol Aspects Med 1995; 16: 215-313.
42. van de Locht A, Lamba D, Bauer M, Huber R, Friedrich T, Kröger B, Höffken W, Bode W. Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin. EMBO J 1995; 14: 5149-57.
43. van de Locht A, Stubbs MT, Bode W, Friedrich T, Bollschweiler C, Höffken W, Huber R. The ornithodorin-thrombin crystal structure, a key to the TAP enigma? EMBO J 1996; 15: 6011-7.
44. Wei A, Alexander RS, Duke J, Ross H, Rosenfeld SA, Chang CH. Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor Xa. J Mol Biol 1998; 283: 147-54.
45. Fuentes-Prior P, Noeske-Jungblut C, Donner P, Schleuning WD, Huber R, Bode W. Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug. Proc Natl Acad Sci U S A 1997; 94: 11845-50.
46. Pechik I, Madrazo J, Mosesson MW, Hernandez I, Gilliland GL, Medved L. Crystal structure of the complex between thrombin and the central "E" region of fibrin. Proc Natl Acad Sci U S A 2004; 101: 2718-23.
47. Stubbs MT, Oschkinat H, Mayr I, Huber R, Angliker H, Stone SR, Bode W. The interaction of thrombin with fibrinogen. A structural basis for its specificity. Eur J Biochem 1992; 206: 187-95.
48. Martin PD, Robertson W, Turk D, Huber R, Bode W, Edwards BF. The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-Å resolution. J Biol Chem 1992; 267: 7911-20.
49. Malkowski MG, Martin PD, Lord ST, Edwards BF. Crystal structure of fibrinogen-Aalpha peptide 1-23 (F8Y) bound to bovine thrombin explains why the mutation of Phe-8 to tyrosine strongly inhibits normal cleavage at Arg-16. Biochem J 1997; 326: 815-22.
50. Sheehan JP, Sadler JE. Molecular mapping of the heparin-binding exosite of thrombin. Proc Natl Acad Sci U S A 1994; 91: 5518-22.
51. Ye J, Rezaie AR, Esmon CT. Glycosaminoglycan contributions to both protein C activation and thrombin inhibition involve a common arginine-rich site in thrombin that includes residues arginine 93, 97, and 101. J Biol Chem 1994; 269: 17965-70.
52. Tsiang M, Jain AK, Gibbs CS. Functional requirements for inhibition of thrombin by antithrombin III in the presence and absence of heparin. J Biol Chem 1997; 272: 12024-9.
53. Carter WJ, Cama E, Huntington JA. Crystal structure of thrombin bound to heparin. J Biol Chem 2005; 280: 2745-9.
54. Li W, Johnson DJ, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol 2004; 11: 857-62.
55. Dementiev A, Petitou M, Herbert JM, Gettins PG. The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity. Nat Struct Mol Biol 2004; 11: 863-7.
56. Ami RK, Padmanabhan K, Padmanabhan KP, Wu TP, Tulinsky A. Structure of the non-covalent complex of prothrombin kringle 2 with PPACK-thrombin. Chem Phys Lipids 1994; 68: 59-66.
57. Martin PD, Malkowski MG, Box J, Esmon CT. New insights into the regulation of the blood clotting cascade derived from the X-ray crystal structure of bovine melzothrombin des F1 in complex with PPACK. Structure 1997; 5: 1681-93.
58. Richardson JL, Kröger B, Hoeffken W, Sadler JE, Pereira P, Huber R, Bode W, Fuentes-Prior P. Crystal structure of the human alpha-thrombin-haemadin complex: an exosite-II binding inhibitor. EMBO J 2000; 19: 5650-60.
59. Richardson JL, Fuentes-Prior P, Sadler JE, Huber R, Bode W. Characterization of the residues involved in the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor. Biochemistry 2002; 41: 2535-42.
60. Ascenzi P, Coletta M, Amiconi G, de Cristofaro R, Bolognesi M, Guarneri M, Menegatti E. Binding of the bovine basic pancreatic trypsin inhibitor (Kunitz) to human alpha-, beta- and gamma-thrombin; a kinetic and thermodynamic study. Biochim Biophys Acta 1988; 956: 156-61.
61. Le Bonniec BF, Esmon CT. Glu-192 - Gln substitution in thrombin mimics the catalytic switch induced by thrombomodulin. Proc Natl Acad Sci U S A 1991; 88: 7371-5.
62. Guinto ER, Ye J, Le Bonniec BF, Esmon CT. Glu192 → Gln substitution in thrombin yields an enzyme that is effectively inhibited by bovine pancreatic trypsin inhibitor and tissue factor pathway inhibitor. J Biol Chem 1994; 269: 18395-400.
63. van de Locht A, Bode W, Huber R, Le Bonniec BF, Stone SR, Esmon CT, Stubbs MT. The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin. EMBO J 1997; 16: 2977-84.
64. Dang QD, Di Cera E. Residue 225 determines the Na(+)-induced allosteric regulation of catalytic activity in serine proteases. Proc Natl Acad Sci U S A 1996; 93: 10653-6.
65. Di Cera E, Guinto ER, Vindigni A, Dang QD, Ayala YM, Wuyi M, Tulinsky A. The Na+ binding site of thrombin. J Biol Chem 1995; 270: 22089-92.
66. Esmon CT, Owen WG. The discovery of thrombomodulin. J Thromb Haemost 2004; 2: 209-13.
67. Ye J, Esmon NL, Esmon CT, Johnson AE. The active site of thrombin is altered upon binding to thrombomodulin. Two distinct structural changes are detected by fluorescence, but only one correlates with protein C activation. J Biol Chem 1991; 266: 23016-21.
68. Wood MJ, Sampoli Benitez BA, Komives EA. Solution structure of the smallest cofactor-active fragment of thrombomodulin. Nat Struct Biol 2000; 7: 200-4.
69. Weisel JW, Nagaswami C, Young TA, Light DR. The shape of thrombomodulin and interactions with thrombin as determined by electron microscopy. J Biol Chem 1996; 271: 31485-90.
70. Fuentes-Prior P, Iwanaga Y, Huber R, Pagila R, Rumennik G, Seto M, Morser J, Light DR, Bode W. Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex. Nature 2000; 404: 518-25.
71. Sampoli Benitez BA, Hunter MJ, Meininger DP, Komives EA. Structure of the fifth EGF-like domain of thrombomodulin: an EGF-like domain with a novel disulfide-bonding pattern. J Mol Biol 1997; 273: 913-26.
72. Nagashima M, Lundh E, Leonard JC, Morser J, Parkinson JF. Alanine-scanning mutagenesis of the epidermal growth factor-like domains of human thrombomodulin identifies critical residues for its cofactor activity. J Biol Chem 1993; 268: 2888-92.
73. Mather T, Oganessyan V, Hof P, Huber R, Foundling S, Esmon C, Bode W. The 2.8 Å crystal structure of Gla-domainless activated protein C. EMBO J 1996; 15: 6822-31.
74. Yang L, Rezaie AR. The fourth epidermal growth factor-like domain of thrombomodulin interacts with the basic exosite of protein C. J Biol Chem 2003; 278: 10484-90.
75. Schneider M, Nagashima M, Knappe S, Zhao L, Morser J, Nesheim M. Amino acid residues in the P6-P'3 region of thrombin-activatable fibrinolysis inhibitor (TAFI) do not determine the thrombomodulin dependence of TAFI activation. J Biol Chem 2002; 277: 9944-51.
76. Overduin M, de Beer T. The plot thickens: how thrombin modulates blood clotting. Nat Struct Biol 2000; 7: 267-9.
77. Krishnaswamy S. Exosite-driven substrate specificity and function in coagulation. J Thromb Haemost 2005; 3: 54-67.
78. Rezaie AR, Yang L. Thrombomodulin allosterically modulates the activity of the anticoagulant thrombin. Proc Natl Acad Sci U S A 2003; 100: 12051-6.
79. Fritz H. Proteases and their inhibitors: traditional research subjects in the Munich area. Biol Chem 2002; 383: 1031-4.
80. 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: 947-66.
81. Brandstetter H, Kuhne A, Bode W, Huber R, von der Saal W, Wirthensohn K, Engh RA. X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition. J Biol Chem 1996; 271: 29988-92.
82. Brandstetter H, Bauer M, Huber R, Lollar P, Bode W. X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B. Proc Natl Acad Sci U S A 1995; 92: 9796-800.
83. Sichler K, Banner DW, D'Arcy A, Hopfner KP, Huber R, Bode W, Kresse GB, Kopetzki E, Brandstetter H. Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions. J Mol Biol 2002; 322: 591-603.
84. Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior P. Crystal structures of the membrane binding C2 domain of human coagulation factor V. Nature 1999; 402: 434-9.
85. Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning WD, Bode W. Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage. Biochemistry 1997; 36: 13483-93.
86. Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W. The 2.3 Å crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator. J Mol Biol 1996; 258: 117-35.
87. Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W. Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA. EMBO J 1997; 16: 4797-805.
88. Parry MA, Fernandez-Catalan C, Bergner A, Huber R, Hopfner KP, Schlott B, Gührs KH, Bode W. The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action. Nat Struct Biol 1998; 5: 917-23.
89. Wang X, Lin X, Loy JA, Tang J, Zhang XC. Crystal structure of the catalytic domain of human plasmin complexed with streptokinase. Science 1998; 281: 1662-5.
90. Wang S, Reed GL, Hedstrom L. Zymogen activation in the streptokinase-plasminogen complex. Ile1 is required for the formation of a functional active site. Eur J Biochem 2000; 267: 3994-4001.
91. Boxrud PD, Verhamme IM, Fay WP, Bock PE. Streptokinase triggers conformational activation of plasminogen through specific interactions of the amino-terminal sequence and stabilizes the active zymogen conformation. J Biol Chem 2001; 276: 26084-9.
92. Terzyan S, Wakeham N, Zhai P, Rodgers K, Zhang XC. Characterization of Lys-698-to-Met substitution in human plasminogen catalytic domain. Proteins 2004; 56: 277-84.
93. Panizzi P, Friedrich R, Fuentes-Prior P, Bode W, Bock PE. The staphylocoagulase family of zymogen activator and adhesion proteins. Cell Mol Life Sci 2004; 61: 2793-8.
94. Friedrich R, Panizzi P, Fuentes-Prior P, Richter K, Verhamme I, Anderson PJ, Kawabata S, Huber R, Bode W, Bock PE. Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation. Nature 2003; 425: 535-9.
95. Pineda AO, Chen ZW, Caccia S, Cantwell AM, Savvides SN, Waksman G, Mathews FS, Di Cera E. The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket. J Biol Chem 2004; 279: 39824-8.
96. Huntington JA, Esmon CT. The molecular basis of thrombin allostery revealed by a 1.8 Å structure of the "slow" form. Structure (Camb) 2003; 11: 469-79.
97. Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA. Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proc Natl Acad Sci U S A 2002; 99: 11079-84.
98. Banner DW, D'Arcy A, Chene C, Winkler FK, Guha A, Konigsberg WH, Nemerson Y, Kirchhofer D. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature 1996; 380: 41-6.
99. Doolittle RF. Determining the crystal structure of fibrinogen. J Thromb Haemost 2004; 2: 683-9.
100. Adams TE, Hockin MF, Mann KG, Everse SJ. The crystal structure of activated protein C-inactivated bovine factor Va: implications for cofactor function. Proc Natl Acad Sci U S A 2004; 101: 8918-23.
101. Huntington JA, Read RJ, Carrell RW. Structure of a serpin-protease complex shows inhibition by deformation. Nature 2000; 407: 923-6.