Thrombin as an anticoagulant

Progress in Molecular Biology and Translational Science

Volumn 99, Issue C, 2011, Pages 145-184

  Di Cera, Enrico ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Allostery; Anticoagulant; Coagulation; Protein C; Protein engineering; Thrombin

Indexed keywords

EID: 78751637342     PISSN: 18771173     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-385504-6.00004-X     Document Type: Chapter

References (189)

1. R.E. Gerszten, and T.J. Wang The search for new cardiovascular biomarkers Nature 451 2008 949 952
2. R.N. Anderson, and B.L. Smith Deaths: leading causes for 2002 Natl Vital Stat Rep 53 2005 1 89
3. V. Padma, M. Fisher, and M. Moonis Thrombolytic therapy for acute ischemic stroke: 3 h and beyond Expert Rev Neurother 5 2005 223 233
4. M. Busch, and F. Masuhr Thromboprophylaxis and early antithrombotic therapy in patients with acute ischemic stroke and cerebral venous and sinus thrombosis Eur J Med Res 9 2004 199 206
5. N. Mackman Triggers, targets and treatments for thrombosis Nature 451 2008 914 918
6. C.T. Esmon The protein C pathway Chest 124 2003 26 32S
7. M. Riewald, R.J. Petrovan, A. Donner, B.M. Mueller, and W. Ruf Activation of endothelial cell protease activated receptor 1 by the protein C pathway Science 296 2002 1880 1882
8. C.S. Gibbs, S.E. Coutre, M. Tsiang, W.X. Li, A.K. Jain, and K.E. Dunn Conversion of thrombin into an anticoagulant by protein engineering Nature 378 1995 413 416
9. A. Gruber, A.M. Cantwell, E. Di Cera, and S.R. Hanson The thrombin mutant W215A/E217A shows safe and potent anticoagulant and antithrombotic effects in vivo J Biol Chem 277 2002 27581 27584
10. A. Gruber, U.M. Marzec, L. Bush, E. Di Cera, J.A. Fernandez, and M.A. Berny Relative antithrombotic and antihemostatic effects of protein C activator versus low molecular weight heparin in primates Blood 109 2007 3733 3740
11. M. Tsiang, L.R. Paborsky, W.X. Li, A.K. Jain, C.T. Mao, and K.E. Dunn Protein engineering thrombin for optimal specificity and potency of anticoagulant activity in vivo Biochemistry 35 1996 16449 16457
12. D. Gailani, and G.J. Broze Jr. Factor XI activation in a revised model of blood coagulation Science 253 1991 909 912
13. T.J. Girard, L.A. MacPhail, K.M. Likert, W.F. Novotny, J.P. Miletich, and G.J. Broze Jr. Inhibition of factor VIIa-tissue factor coagulation activity by a hybrid protein Science 248 1990 1421 1424
14. K.G. Mann, S. Butenas, and K. Brummel The dynamics of thrombin formation Arterioscler Thromb Vasc Biol 23 2003 17 25
15. E. Di Cera Thrombin Mol Aspects Med 29 2008 203 254
16. E.W. Davie, and J.D. Kulman An overview of the structure and function of thrombin Semin Thromb Hemost 32 Suppl. 1 2006 3 15
17. W. Bode Structure and interaction modes of thrombin Blood Cells Mol Dis 36 2006 122 130
18. D.A. Lane, H. Philippou, and J.A. Huntington Directing thrombin Blood 106 2005 2605 2612
19. E. Di Cera, E.R. Guinto, A. Vindigni, Q.D. Dang, Y.M. Ayala, and M. Wuyi The Na+ binding site of thrombin J Biol Chem 270 1995 22089 22092
20. A.O. Pineda, C.J. Carrell, L.A. Bush, S. Prasad, S. Caccia, and Z.W. Chen Molecular dissection of Na+ binding to thrombin J Biol Chem 279 2004 31842 31853
21. Q.D. Dang, and E. Di Cera Residue 225 determines the Na(+)-induced allosteric regulation of catalytic activity in serine proteases Proc Natl Acad Sci USA 93 1996 10653 10656
22. Y.M. Ayala, A.M. Cantwell, T. Rose, L.A. Bush, D. Arosio, and E. Di Cera Molecular mapping of thrombin-receptor interactions Proteins 45 2001 107 116
23. O.D. Dang, A. Vindigni, and E. Di Cera An allosteric switch controls the procoagulant and anticoagulant activities of thrombin Proc Natl Acad Sci USA 92 1995 5977 5981
24. Q.D. Dang, E.R. Guinto, and E. Di Cera Rational engineering of activity and specificity in a serine protease Nat Biotechnol 15 1997 146 149
25. S.R. Coughlin Thrombin signalling and protease-activated receptors Nature 407 2000 258 264
26. S.R. Coughlin Protease-activated receptors in hemostasis, thrombosis and vascular biology J Thromb Haemost 3 2005 1800 1814
27. E. Di Cera Thrombin as procoagulant and anticoagulant J Thromb Haemost 5 2007 196 202
28. T. Myles, T.H. Yun, S.W. Hall, and L.L. Leung An extensive interaction interface between thrombin and factor V is required for factor V activation J Biol Chem 276 2001 25143 25149
29. K. Nogami, Q. Zhou, T. Myles, L.L. Leung, H. Wakabayashi, and P.J. Fay Exosite-interactive regions in the A1 and A2 domains of factor VIII facilitate thrombin-catalyzed cleavage of heavy chain J Biol Chem 280 2005 18476 18487
30. T.H. Yun, F.A. Baglia, T. Myles, D. Navaneetham, J.A. Lopez, and P.N. Walsh Thrombin activation of factor XI on activated platelets requires the interaction of factor XI and platelet glycoprotein Ib alpha with thrombin anion-binding exosites I and II, respectively J Biol Chem 278 2003 48112 48119
31. K.G. Mann Thrombin formation Chest 124 2003 4S 10S
32. S.J. Degen, S.A. McDowell, L.M. Sparks, and I. Scharrer Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala Thromb Haemost 73 1995 203 209
33. T. Miyata, R. Aruga, H. Umeyama, A. Bezeaud, M.C. Guillin, and S. Iwanaga Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity Biochemistry 31 1992 7457 7462
34. R.A. Henriksen, C.K. Dunham, L.D. Miller, J.T. Casey, J.B. Menke, and C.L. Knupp Prothrombin Greenville, Arg517>Gln, identified in an individual heterozygous for dysprothrombinemia Blood 91 1998 2026 2031
35. W.Y. Sun, D. Smirnow, M.L. Jenkins, and S.J. Degen Prothrombin Scranton: substitution of an amino acid residue involved in the binding of Na+ (LYS-556 to THR) leads to dysprothrombinemia Thromb Haemost 85 2001 651 654
36. H. Stanchev, M. Philips, B.O. Villoutreix, L. Aksglaede, S. Lethagen, and S. Thorsen Prothrombin deficiency caused by compound heterozigosity for two novel mutations in the prothrombin gene associated with a bleeding tendency Thromb Haemost 95 2006 195 198
37. S. Rouy, D. Vidaud, J.L. Alessandri, M.D. Dautzenberg, L. Venisse, and M.C. Guillin Prothrombin Saint-Denis: a natural variant with a point mutation resulting in Asp to Glu substitution at position 552 in prothrombin Br J Haematol 132 2006 770 773
38. A.M. Cantwell, and E. Di Cera Rational design of a potent anticoagulant thrombin J Biol Chem 275 2000 39827 39830
39. A. Bah, C.J. Carrell, Z. Chen, P.S. Gandhi, and E. Di Cera Stabilization of the E* form turns thrombin into an anticoagulant J Biol Chem 284 2009 20034 20040
40. M.A. Berny, T.C. White, E.I. Tucker, L.A. Bush-Pelc, E. Di Cera, and A. Gruber Thrombin mutant W215A/E217A acts as a platelet GpIb antagonist Arterioscler Thromb Vasc Biol 18 2008 329 334
41. A. Gruber, J.A. Fernandez, L. Bush, U. Marzec, J.H. Griffin, and S.R. Hanson Limited generation of activated protein C during infusion of the protein C activator thrombin analog W215A/E217A in primates J Thromb Haemost 4 2006 392 397
42. S.M. Bates, and J.I. Weitz The status of new anticoagulants Br J Haematol 134 2006 3 19
43. M.F. Doyle, and K.G. Mann Multiple active forms of thrombin. IV. Relative activities of meizothrombins J Biol Chem 265 1990 10693 10701
44. W. Bode, D. Turk, and A. Karshikov The refined 1.9-A 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 1 1992 426 471
45. T.C. Hageman, G.F. Endres, and H.A. Scheraga Mechanism of action of thrombin on fibrinogen. On the role of the A chain of bovine thrombin in specificity and in differentiating between thrombin and trypsin Arch Biochem Biophys 171 1975 327 336
46. E.E. DiBella, M.C. Maurer, and H.A. Scheraga Expression and folding of recombinant bovine prethrombin-2 and its activation to thrombin J Biol Chem 270 1995 163 169
47. J.B. Lefkowitz, T. Haver, S. Clarke, L. Jacobson, A. Weller, and R. Nuss The prothrombin Denver patient has two different prothrombin point mutations resulting in Glu-300>Lys and Glu-309>Lys substitutions Br J Haematol 108 2000 182 187
48. S. Akhavan, P.M. Mannucci, M. Lak, G. Mancuso, M.G. Mazzucconi, and A. Rocino Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency Thromb Haemost 84 2000 989 997
49. S. Akhavan, E. Rocha, S. Zeinali, and P.M. Mannucci Gly319 > arg substitution in the dysfunctional prothrombin Segovia Br J Haematol 105 1999 667 669
50. W.Y. Sun, M.C. Burkart, J.R. Holahan, and S.J. Degen Prothrombin San Antonio: a single amino acid substitution at a factor Xa activation site (Arg320 to His) results in dysprothrombinemia Blood 95 2000 711 714
51. R. De Cristofaro, S. Akhavan, C. Altomare, A. Carotti, F. Peyvandi, and P.M. Mannucci A natural prothrombin mutant reveals an unexpected influence of a-chain structure on the activity of human {alpha}-thrombin J Biol Chem 279 2004 13035 13043
52. R. De Cristofaro, A. Carotti, S. Akhavan, R. Palla, F. Peyvandi, and C. Altomare The natural mutation by deletion of Lys9 in the thrombin A-chain affects the pKa value of catalytic residues, the overall enzyme's stability and conformational transitions linked to Na+ binding FEBS J 273 2006 159 169
53. M.E. Papaconstantinou, A. Bah, and E. Di Cera Role of the A chain in thrombin function Cell Mol Life Sci 65 2008 1943 1947
54. I. Schechter, and A. Berger On the size of the active site in proteases. I. Papain Biochem Biophys Res Commun 27 1967 157 162
55. L.A. Bush, R.W. Nelson, and E. Di Cera Murine thrombin lacks Na+ activation but retains high catalytic activity J Biol Chem 281 2006 7183 7188
56. C.J. Martin, J. Golubow, and A.E. Axelrod The hydrolysis of carbobenzoxy-L-tyrosine p-nitrophenyl ester by various enzymes J Biol Chem 234 1959 1718 1725
57. L. Lorand, W.T. Brannen Jr., and N.G. Rule Thrombin-catalyzed hydrolysis of p-nitrophenyl esters Arch Biochem Biophys 96 1962 147 151
58. F.J. Kezdy, L. Lorand, and K.D. Miller Titration of active centers in thrombin solutions. Standardization of the enzyme Biochemistry 4 1965 2302 2308
59. D.B. Cleary, T.A. Trumbo, and M.C. Maurer Protease-activated receptor 4-like peptides bind to thrombin through an optimized interaction with the enzyme active site surface Arch Biochem Biophys 403 2002 179 188
60. P.S. Gandhi, Z. Chen, and E. Di Cera Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1 J Biol Chem 285 2010 15393 15398
61. Q.D. Dang, M. Sabetta, and E. Di Cera Selective loss of fibrinogen clotting in a loop-less thrombin J Biol Chem 272 1997 19649 19651
62. H.D. Bartunik, L.J. Summers, and H.H. Bartsch Crystal structure of bovine beta-trypsin at 1.5 A resolution in a crystal form with low molecular packing density. Active site geometry, ion pairs and solvent structure J Mol Biol 210 1989 813 828
63. L. Yang, S. Prasad, E. Di Cera, and A.R. Rezaie The conformation of the activation peptide of protein C is influenced by Ca2+ and Na+ binding J Biol Chem 279 2004 38519 38524
64. M. Tsiang, A.K. Jain, K.E. Dunn, M.E. Rojas, L.L. Leung, and C.S. Gibbs Functional mapping of the surface residues of human thrombin J Biol Chem 270 1995 16854 16863
65. I. Pechik, J. Madrazo, M.W. Mosesson, I. Hernandez, G.L. Gilliland, and L. Medved Crystal structure of the complex between thrombin and the central "E" region of fibrin Proc Natl Acad Sci USA 101 2004 2718 2723
66. I. Pechik, S. Yakovlev, M.W. Mosesson, G.L. Gilliland, and L. Medved Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly Biochemistry 45 2006 3588 3597
67. S.W. Hall, M. Nagashima, L. Zhao, J. Morser, and L.L. Leung Thrombin interacts with thrombomodulin, protein C, and thrombin-activatable fibrinolysis inhibitor via specific and distinct domains J Biol Chem 274 1999 25510 25516
68. P. Fuentes-Prior, Y. Iwanaga, R. Huber, R. Pagila, G. Rumennik, and M. Seto Structural basis for the anticoagulant activity of the thrombin- thrombomodulin complex Nature 404 2000 518 525
69. A.O. Pineda, A.M. Cantwell, L.A. Bush, T. Rose, and E. Di Cera The thrombin epitope recognizing thrombomodulin is a highly cooperative hot spot in exosite I J Biol Chem 277 2002 32015 32019
70. H. Xu, L.A. Bush, A.O. Pineda, S. Caccia, and E. Di Cera Thrombomodulin changes the molecular surface of interaction and the rate of complex formation between thrombin and protein C J Biol Chem 280 2005 7956 7961
71. T.K. Vu, V.I. Wheaton, D.T. Hung, I. Charo, and S.R. Coughlin Domains specifying thrombin-receptor interaction Nature 353 1991 674 677
72. T. Myles, B.F. Le Bonniec, and S.R. Stone The dual role of thrombin's anion-binding exosite-I in the recognition and cleavage of the protease-activated receptor 1 Eur J Biochem 268 2001 70 77
73. H. Ishihara, A.J. Connolly, D. Zeng, M.L. Kahn, Y.W. Zheng, and C. Timmons Protease-activated receptor 3 is a second thrombin receptor in humans Nature 386 1997 502 506
74. Z.R. Gan, Y. Li, Z. Chen, S.D. Lewis, and J.A. Shafer Identification of basic amino acid residues in thrombin essential for heparin-catalyzed inactivation by antithrombin III J Biol Chem 269 1994 1301 1305
75. J.P. Sheehan, and J.E. Sadler Molecular mapping of the heparin-binding exosite of thrombin Proc Natl Acad Sci USA 91 1994 5518 5522
76. M. Tsiang, A.K. Jain, and C.S. Gibbs Functional requirements for inhibition of thrombin by antithrombin III in the presence and absence of heparin J Biol Chem 272 1997 12024 12029
77. W. Li, D.J. Johnson, C.T. Esmon, and J.A. Huntington Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin Nat Struct Mol Biol 11 2004 857 862
78. W.J. Carter, E. Cama, and J.A. Huntington Crystal structure of thrombin bound to heparin J Biol Chem 280 2005 2745 2749
79. P.D. Martin, M.G. Malkowski, J. Box, C.T. Esmon, and B.F. Edwards New insights into the regulation of the blood clotting cascade derived from the X-ray crystal structure of bovine meizothrombin des F1 in complex with PPACK Structure 5 1997 1681 1693
80. M.E. Papaconstantinou, P.S. Gandhi, Z. Chen, A. Bah, and E. Di Cera Na(+) binding to meizothrombin desF1 Cell Mol Life Sci 65 2008 3688 3697
81. S.T. Olson, and Y.J. Chuang Heparin activates antithrombin anticoagulant function by generating new interaction sites (exosites) for blood clotting proteinases Trends Cardiovasc Med 12 2002 331 338
82. P.G. Gettins Serpin structure, mechanism, and function Chem Rev 102 2002 4751 4804
83. A. Dementiev, M. Petitou, J.M. Herbert, and P.G. Gettins The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity Nat Struct Mol Biol 11 2004 863 867
84. R. De Cristofaro, E. De Candia, S. Rutella, and J.I. Weitz The Asp(272)-Glu(282) region of platelet glycoprotein Ibalpha interacts with the heparin-binding site of alpha-thrombin and protects the enzyme from the heparin-catalyzed inhibition by antithrombin III J Biol Chem 275 2000 3887 3895
85. R. Celikel, R.A. McClintock, J.R. Roberts, G.L. Mendolicchio, J. Ware, and K.I. Varughese Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Ibalpha Science 301 2003 218 221
86. J.J. Dumas, R. Kumar, J. Seehra, W.S. Somers, and L. Mosyak Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation Science 301 2003 222 226
87. V. Ramakrishnan, F. DeGuzman, M. Bao, S.W. Hall, L.L. Leung, and D.R. Phillips A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V Proc Natl Acad Sci USA 98 2001 1823 1828
88. A.O. Pineda, Z.W. Chen, F. Marino, F.S. Mathews, M.W. Mosesson, and E. Di Cera Crystal structure of thrombin in complex with fibrinogen gamma' peptide Biophys Chem 125 2007 556 559
89. N.S. Colwell, M.A. Blinder, M. Tsiang, C.S. Gibbs, P.E. Bock, and D.M. Tollefsen Allosteric effects of a monoclonal antibody against thrombin exosite II Biochemistry 37 1998 15057 15065
90. E. Di Cera A structural perspective on enzymes activated by monovalent cations J Biol Chem 281 2006 1305 1308
91. S. Prasad, K.J. Wright, D.B. Roy, L.A. Bush, A.M. Cantwell, and E. Di Cera Redesigning the monovalent cation specificity of an enzyme Proc Natl Acad Sci USA 100 2003 13785 13790
92. E. Zhang, and A. Tulinsky The molecular environment of the Na+ binding site of thrombin Biophys Chem 63 1997 185 200
93. K. Scharer, M. Morgenthaler, R. Paulini, U. Obst-Sander, D.W. Banner, and D. Schlatter Quantification of cation-pi interactions in protein-ligand complexes: crystal-structure analysis of Factor Xa bound to a quaternary ammonium ion ligand Angew Chem Int Ed Engl 44 2005 4400 4404
94. 2+ sites in factor VIIa J Biol Chem 281 2006 24873 24888
95. 2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops J Biol Chem 277 2002 28987 28995
96. T. Zogg, and H. Brandstetter Structural basis of the cofactor- and substrate-assisted activation of human coagulation factor IXa Structure 17 2009 1669 1678
97. R.J. Petrovan, and W. Ruf Role of residue Phe225 in the cofactor-mediated, allosteric regulation of the serine protease coagulation factor VIIa Biochemistry 39 2000 14457 14463
98. A.E. Schmidt, J.E. Stewart, A. Mathur, S. Krishnaswamy, and S.P. Bajaj Na+ site in blood coagulation factor IXa: effect on catalysis and factor VIIIa binding J Mol Biol 350 2005 78 91
99. K. Gopalakrishna, and A.R. Rezaie The influence of sodium ion binding on factor IXa activity Thromb Haemost 95 2006 936 941
100. A.R. Rezaie, and X. He Sodium binding site of factor Xa: role of sodium in the prothrombinase complex Biochemistry 39 2000 1817 1825
101. A.R. Rezaie, and F.S. Kittur The critical role of the 185-189-loop in the factor Xa interaction with Na+ and factor Va in the prothrombinase complex J Biol Chem 279 2004 48262 48269
102. C.L. Orthner, and D.P. Kosow The effect of metal ions on the amidolytic acitivity of human factor Xa (activated Stuart-Prower factor) Arch Biochem Biophys 185 1978 400 406
103. D. Monnaie, D. Arosio, N. Griffon, T. Rose, A.R. Rezaie, and E. Di Cera Identification of a binding site for quaternary amines in factor Xa Biochemistry 39 2000 5349 5354
104. M.C. Underwood, D. Zhong, A. Mathur, T. Heyduk, and S.P. Bajaj Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human coagulation factor xa. Studies on catalytic efficiency and inhibitor binding J Biol Chem 275 2000 36876 36884
105. R.M. Camire Prothrombinase assembly and S1 site occupation restore the catalytic activity of FXa impaired by mutation at the sodium-binding site J Biol Chem 277 2002 37863 37870
106. S. Levigne, F. Thiec, S. Cherel, J.A. Irving, C. Fribourg, and O.D. Christophe Role of the alpha-helix 163-170 in factor Xa catalytic activity J Biol Chem 282 2007 31569 31579
107. X. He, and A.R. Rezaie Identification and characterization of the sodium-binding site of activated protein C J Biol Chem 274 1999 4970 4976
108. S.A. Steiner, G.W. Amphlett, and F.J. Castellino Stimulation of the amidase and esterase activity of activated bovine plasma protein C by monovalent cations Biochem Biophys Res Commun 94 1980 340 347
109. S.A. Steiner, and F.J. Castellino Kinetic studies of the role of monovalent cations in the amidolytic activity of activated bovine plasma protein C Biochemistry 21 1982 4609 4614
110. S.A. Steiner, and F.J. Castellino Effect of monovalent cations on the pre-steady-state kinetic parameters of the plasma protease bovine activated protein C Biochemistry 24 1985 1136 1141
111. S.A. Steiner, and F.J. Castellino Kinetic mechanism for stimulation by monovalent cations of the amidase activity of the plasma protease bovine activated protein C Biochemistry 24 1985 609 617
112. B.W. Grinnell Tipping the balance of blood coagulation Nat Biotechnol 15 1997 124 125
113. M.J. Page, and E. Di Cera Is Na+ a coagulation factor? Thromb Haemost 95 2006 920 921
114. J.A. Huntington Molecular recognition mechanisms of thrombin J Thromb Haemost 3 2005 1861 1872
115. M.J. Page, R.T.A. MacGillivray, and E. Di Cera Determinants of specificity in coagulation proteases J Thromb Haemost 3 2005 2401 2408
116. S. Krishnaswamy Exosite-driven substrate specificity and function in coagulation J Thromb Haemost 3 2005 54 67
117. S. Krishnaswamy, and A. Betz Exosites determine macromolecular substrate recognition by prothrombinase Biochemistry 36 1997 12080 12086
118. J.J. Perona, and C.S. Craik Structural basis of substrate specificity in the serine proteases Protein Sci 4 1995 337 360
119. J.J. Perona, and C.S. Craik Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold J Biol Chem 272 1997 29987 29990
120. L. Hedstrom Serine protease mechanism and specificity Chem Rev 102 2002 4501 4524
121. M.T. Stubbs, H. Oschkinat, I. Mayr, R. Huber, H. Angliker, and S.R. Stone The interaction of thrombin with fibrinogen. A structural basis for its specificity Eur J Biochem 206 1992 187 195
122. A. Bah, Z. Chen, L.A. Bush-Pelc, F.S. Mathews, and E. Di Cera Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4 Proc Natl Acad Sci USA 104 2007 11603 11608
123. C. Sadasivan, and V.C. Yee Interaction of the factor XIII activation peptide with alpha-thrombin. Crystal structure of its enzyme-substrate analog complex J Biol Chem 275 2000 36942 36948
124. T.J. Rydel, A. Tulinsky, W. Bode, and R. Huber Refined structure of the hirudin-thrombin complex J Mol Biol 221 1991 583 601
125. J. Vijayalakshmi, K.P. Padmanabhan, K.G. Mann, and A. Tulinsky The isomorphous structures of prethrombin2, hirugen-, and PPACK-thrombin: changes accompanying activation and exosite binding to thrombin Protein Sci 3 1994 2254 2271
126. T. Rose, and E. Di Cera Three-dimensional modeling of thrombin-fibrinogen interaction J Biol Chem 277 2002 18875 18880
127. I.I. Mathews, K.P. Padmanabhan, V. Ganesh, A. Tulinsky, M. Ishii, and J. Chen Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes Biochemistry 33 1994 3266 3279
128. T.P. Baglin, R.W. Carrell, F.C. Church, C.T. Esmon, and J.A. Huntington Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism Proc Natl Acad Sci USA 99 2002 11079 11084
129. E. Di Cera, M.J. Page, A. Bah, L.A. Bush-Pelc, and L.C. Garvey Thrombin allostery Phys Chem Chem Phys 9 2007 1292 1306
130. C.M. Wells, and E. Di Cera Thrombin is a Na(+)-activated enzyme Biochemistry 31 1992 11721 11730
131. N. Griffon, and E. Di Stasio Thermodynamics of Na+ binding to coagulation serine proteases Biophys Chem 90 2001 89 96
132. E.R. Guinto, and E. Di Cera Large heat capacity change in a protein-monovalent cation interaction Biochemistry 35 1996 8800 8804
133. A. Bah, L.C. Garvey, J. Ge, and E. Di Cera Rapid kinetics of Na+ binding to thrombin J Biol Chem 281 2006 40049 40056
134. J. Botts, and M. Morales Analytical description of the effects of modifiers and of multivalency upon the steady state catalyzed reaction rate Trans Faraday Soc 49 1953 696 707
135. S. Gianni, Y. Ivarsson, A. Bah, L.A. Bush-Pelc, and E. Di Cera Mechanism of Na+ binding to thrombin resolved by ultra-rapid kinetics Biophys Chem 131 2007 111 114
136. M.T. Lai, E. Di Cera, and J.A. Shafer Kinetic pathway for the slow to fast transition of thrombin. Evidence of linked ligand binding at structurally distinct domains J Biol Chem 272 1997 30275 30282
137. W. Niu, Z. Chen, L.A. Bush-Pelc, A. Bah, P.S. Gandhi, and E. Di Cera Mutant N143P reveals how Na+ activates thrombin J Biol Chem 284 2009 36175 36185
138. M.J. Page, and E. Di Cera Role of Na+ and K+ in enzyme function Physiol Rev 86 2006 1049 1092
139. A.O. Pineda, S.N. Savvides, G. Waksman, and E. Di Cera Crystal structure of the anticoagulant slow form of thrombin J Biol Chem 277 2002 40177 40180
140. A.O. Pineda, E. Zhang, E.R. Guinto, S.N. Savvides, A. Tulinsky, and E. Di Cera Crystal structure of the thrombin mutant D221A/D222K: the Asp222:Arg187 ion-pair stabilizes the fast form Biophys Chem 112 2004 253 256
141. F. Marino, Z.W. Chen, C. Ergenekan, L.A. Bush-Pelc, F.S. Mathews, and E. Di Cera Structural basis of Na+ activation mimicry in murine thrombin J Biol Chem 282 2007 16355 16361
142. S. Prasad, A.M. Cantwell, L.A. Bush, P. Shih, H. Xu, and E. Di Cera Residue Asp-189 controls both substrate binding and the monovalent cation specificity of thrombin J Biol Chem 279 2004 10103 10108
143. D.T. Berg, M.R. Wiley, and B.W. Grinnell Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator Science 273 1996 1389 1391
144. A.R. Rezaie, and S.T. Olson Contribution of lysine 60f to S1' specificity of thrombin Biochemistry 36 1997 1026 1033
145. C.N. Fuhrmann, M.D. Daugherty, and D.A. Agard Subangstrom crystallography reveals that short ionic hydrogen bonds, and not a His-Asp low-barrier hydrogen bond, stabilize the transition state in serine protease catalysis J Am Chem Soc 128 2006 9086 9102
146. D.J. Johnson, T.E. Adams, W. Li, and J.A. Huntington Crystal structure of wild-type human thrombin in the Na +-free state Biochem J 392 2005 21 28
147. P.S. Gandhi, Z. Chen, F.S. Mathews, and E. Di Cera Structural identification of the pathway of long-range communication in an allosteric enzyme Proc Natl Acad Sci USA 105 2008 1832 1837
148. A.O. Pineda, Z.W. Chen, A. Bah, L.C. Garvey, F.S. Mathews, and E. Di Cera Crystal structure of thrombin in a self-inhibited conformation J Biol Chem 281 2006 32922 32928
149. H. Fehlhammer, W. Bode, and R. Huber Crystal structure of bovine trypsinogen at 1-8 A resolution. II. Crystallographic refinement, refined crystal structure and comparison with bovine trypsin J Mol Biol 111 1977 415 438
150. D. Wang, W. Bode, and R. Huber Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 A resolution J Mol Biol 185 1985 595 624
151. K.K. Reiling, J. Krucinski, L.J. Miercke, W.W. Raymond, G.H. Caughey, and R.M. Stroud Structure of human pro-chymase: a model for the activating transition of granule-associated proteases Biochemistry 42 2003 2616 2624
152. R. Friedrich, P. Panizzi, P. Fuentes-Prior, K. Richter, I. Verhamme, and P.J. Anderson Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation Nature 425 2003 535 539
153. A.R. Fersht Conformational equilibria in -and -chymotrypsin. The energetics and importance of the salt bridge J Mol Biol 64 1972 497 509
154. A.R. Fersht, and Y. Requena Equilibrium and rate constants for the interconversion of two conformations of -chymotrypsin. The existence of a catalytically inactive conformation at neutral pH J Mol Biol 60 1971 279 290
155. K.B. Rohr, T. Selwood, U. Marquardt, R. Huber, N.M. Schechter, and W. Bode X-ray structures of free and leupeptin-complexed human alphaI-tryptase mutants: indication for an alpha>beta-tryptase transition J Mol Biol 357 2006 195 209
156. T. Krojer, M. Garrido-Franco, R. Huber, M. Ehrmann, and T. Clausen Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine Nature 416 2002 455 459
157. H. Jing, Y.S. Babu, D. Moore, J.M. Kilpatrick, X.Y. Liu, and J.E. Volanakis Structures of native and complexed complement factor D: implications of the atypical His57 conformation and self-inhibitory loop in the regulation of specific serine protease activity J Mol Biol 282 1998 1061 1081
158. C. Hink-Schauer, E. Estebanez-Perpina, E. Wilharm, P. Fuentes-Prior, W. Klinkert, and W. Bode The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features J Biol Chem 277 2002 50923 50933
159. S. Shia, J. Stamos, D. Kirchhofer, B. Fan, J. Wu, and R.T. Corpuz Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B J Mol Biol 346 2005 1335 1349
160. A.L. Carvalho, L. Sanz, D. Barettino, A. Romero, J.J. Calvete, and M.J. Romao Crystal structure of a prostate kallikrein isolated from stallion seminal plasma: a homologue of human PSA J Mol Biol 322 2002 325 337
161. K.W. Rickert, P. Kelley, N.J. Byrne, R.E. Diehl, D.L. Hall, and A.M. Montalvo Structure of human prostasin, a target for the regulation of hypertension J Biol Chem 283 2008 34864 34872
162. G. Spraggon, M. Hornsby, A. Shipway, D.C. Tully, B. Bursulaya, and H. Danahay Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations Protein Sci 18 2009 1081 1094
163. K. Ponnuraj, Y. Xu, K. Macon, D. Moore, J.E. Volanakis, and S.V. Narayana Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase Mol Cell 14 2004 17 28
164. I.H. Barrette-Ng, K.K. Ng, B.L. Mark, D. Van Aken, M.M. Cherney, and C. Garen Structure of arterivirus nsp4. The smallest chymotrypsin-like proteinase with an alpha/beta C-terminal extension and alternate conformations of the oxyanion hole J Biol Chem 277 2002 39960 39966
165. J. Cavarelli, G. Prevost, W. Bourguet, L. Moulinier, B. Chevrier, and B. Delagoutte The structure of Staphylococcus aureus epidermolytic toxin A, an atypic serine protease, at 1.7 A resolution Structure 5 1997 813 824
166. G.M. Vath, C.A. Earhart, J.V. Rago, M.H. Kim, G.A. Bohach, and P.M. Schlievert The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease Biochemistry 36 1997 1559 1566
167. E. Di Cera Serine proteases IUBMB Life 61 2009 510 515
168. Q.Y. Wu, J.P. Sheehan, M. Tsiang, S.R. Lentz, J.J. Birktoft, and J.E. Sadler Single amino acid substitutions dissociate fibrinogen-clotting and thrombomodulin-binding activities of human thrombin Proc Natl Acad Sci USA 88 1991 6775 6779
169. F. Marino, L.A. Pelc, A. Vogt, P.S. Gandhi, and E. Di Cera Engineering thrombin for selective specificity toward protein C and PAR1 J Biol Chem 285 2010 19145 19152
170. D. Arosio, Y.M. Ayala, and E. Di Cera Mutation of W215 compromises thrombin cleavage of fibrinogen, but not of PAR-1 or protein C Biochemistry 39 2000 8095 8101
171. C. Feistritzer, R.A. Schuepbach, L.O. Mosnier, L.A. Bush, E. Di Cera, and J.H. Griffin Protective signaling by activated protein C is mechanistically linked to protein C activation on endothelial cells J Biol Chem 281 2006 20077 20084
172. A. Gruber, J.H. Griffin, L.A. Harker, and S.R. Hanson Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model Blood 73 1989 639 642
173. A. Gruber, S.R. Hanson, A.B. Kelly, B.S. Yan, N. Bang, and J.H. Griffin Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis Circulation 82 1990 578 585
174. F.B. Taylor, A. Chang, C.T. Esmon, A. D'Angelo, S. Vigano-D'Angelo, and K.E. Blick Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon J Clin Invest 79 1987 918 925
175. G.R. Bernard, J.L. Vincent, P.F. Laterre, S.P. LaRosa, J.F. Dhainaut, and A. Lopez-Rodriguez Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis N Engl J Med 344 2001 699 709
176. F.B. Taylor Jr., G.T. Peer, M.S. Lockhart, G. Ferrell, and C.T. Esmon Endothelial cell protein C receptor plays an important role in protein C activation in vivo Blood 97 2001 1685 1688
177. C.T. Esmon, J. Xu, J.M. Gu, D. Qu, Z. Laszik, and G. Ferrell Endothelial protein C receptor Thromb Haemost 82 1999 251 258
178. J.S. Bae, L. Yang, C. Manithody, and A.R. Rezaie The ligand occupancy of endothelial protein C receptor switches the protease-activated receptor 1-dependent signaling specificity of thrombin from a permeability-enhancing to a barrier-protective response in endothelial cells Blood 110 2007 3909 3916
179. J.S. Bae, L. Yang, and A.R. Rezaie Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of
180. S.R. Hanson, J.H. Griffin, L.A. Harker, A.B. Kelly, C.T. Esmon, and A. Gruber Antithrombotic effects of thrombin-induced activation of endogenous protein C in primates J Clin Invest 92 1993 2003 2012
181. J.H. Griffin Blood coagulation. The thrombin paradox Nature 378 1995 337 338
182. W.J. Carter, T. Myles, C.S. Gibbs, L.L. Leung, and J.A. Huntington Crystal structure of anticoagulant thrombin variant E217K provides insights into thrombin allostery J Biol Chem 279 2004 26387 26394
183. A.O. Pineda, Z.W. Chen, S. Caccia, A.M. Cantwell, S.N. Savvides, and G. Waksman The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket J Biol Chem 279 2004 39824 39828
184. E.E. DiBella, and H.A. Scheraga The role of the insertion loop around tryptophan 148 in tthe activity of thrombin Biochemistry 35 1996 4427 4433
185. B.F. Le Bonniec, E.R. Guinto, and C.T. Esmon Interaction of thrombin des-ETW with antithrombin III, the Kunitz inhibitors, thrombomodulin and protein C. Structural link between the autolysis loop and the Tyr-Pro-Pro-Trp insertion of thrombin J Biol Chem 267 1992 19341 19348
186. A. Vindigni, C.E. White, E.A. Komives, and E. Di Cera Energetics of thrombin-thrombomodulin interaction Biochemistry 36 1997 6674 6681
187. P.S. Gandhi, M.J. Page, Z. Chen, L.A. Bush-Pelc, and E. Di Cera Mechanism of the anticoagulant activity of the thrombin mutant W215A/E217A J Biol Chem 284 2009 24098 24105
188. M.J. Page, and E. Di Cera Serine peptidases: classification, structure and function Cell Mol Life Sci 65 2008 1220 1236
189. G. Isetti, and M.C. Maurer Employing mutants to study thrombin residues responsible for factor XIII activation peptide recognition: a kinetic study Biochemistry 46 2007 2444 2452