Structural biology of factor VIIa/tissue factor initiated coagulation

Frontiers in Bioscience

Volumn 17, Issue 7, 2011, Pages 2476-2494

  Vadivel, Kanagasabai ^a   Bajaj, S Paul ^a,b  

^a JOINT REPLACEMENT INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Blood coagulation; Factor VIIa; Factors IX and X*Structural biology; Review; Tissue factor

Indexed keywords

EID: 84860294702     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/4066     Document Type: Article

References (108)

1. G. J. Broze Jr and P. W. Majerus: Purification and properties of human coagulation factor VII. J Biol Chem 255, 1242-1247 (1980) (Pubitemid 10111981)
2. S. P. Bajaj, S.I. Rapaport and S. F. Brown: Isolation and characterization of human factor VII. Activation of factor VII by factor Xa. J Biol Chem 256, 253-259 (1981) (Pubitemid 12207111)
3. D. L. Greenberg and E. W. Davie: The blood coagulation factors-their complementary DNAs, genes, and expression, Chapter 3, 21-57; in Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Eds. R. W. Colman, V. J. Marder, A. W. Clowes, J. N. George and S. Z. Goldhaber; New York: Lippincott Williams and Wilkins (2006)
4. Y. Nemerson and D. Repke: Tissue factor accelerates the activation of coagulation factor VII: the role of a bifunctional coagulation cofactor. Thromb Res 40, 351-358 (1985) (Pubitemid 16181507)
5. L. V. M. Rao and S. I. Rapaport: Activation of factor VII bound to tissue factor-A key early step in the tissue factor pathway of blood coagulation. Proc Natl Acad Sci USA 85, 6687-6691 (1988)
6. E. B. Williams, S. Krishnaswamy and K. G. Mann: Zymogen/enzyme discriminations using peptide chloromethyl ketones. J Biol Chem 264, 7536-7545 (1989) (Pubitemid 19119171)
7. P. Wildgoose, K. L. Berkner and W. Kisiel: Synthesis, purification and characterization of an Arg152Glu sitedirected mutant of recombinant human blood clotting factor VII. Biochemistry 29, 3413-3420 (1990) (Pubitemid 20131489)
8. R. Radcliffe and Y. Nemerson: Activation and control of factor VII by activated factor X and thrombin. J Biol Chem 250, 388-395 (1975)
9. L. V. M. Rao, S. P. Bajaj and S. I. Rapaport: Activation of factor VII during clotting in vitro. Blood 65, 218-226 (1985) (Pubitemid 15191062)
10. T. Nagagaki, D. C. Foster, K. L. Berkner, W. Kisiel: Initiation of the extrinsic pathway of blood coagulation-Evidence for the tissue factor dependent autoactivation of human coagulation factor VII. Biochemistry 30, 10819-10824 (1991)
11. P. F. Neuenschwander, M. M. Fiore and J. H. Morrissey: Factor VII autoactivation proceeds via interaction of distinct protease-cofactor and zymogencofactor complexes. J Biol Chem 268, 21489-21492 (1993)
12. S. Butenas and K. G. Mann: Kinetics of human factor VII activation. Biochemistry 35, 1904-1910 (1996) (Pubitemid 26062639)
13. J. F. Bazan: Structural design and molecular evaluation of a cytokine receptor superfamily. Proc Natl Acad Sci USA 87, 6934-6938 (1990)
14. K. Harlos, D. M. A. Martin, D. P. O'Brien, E. Y. Jones, D. Stuart, D. I. Polikarpov, A. Miller, E. G. D. Tuddenham and C. W. G. Boys: Crystal structure of the extracellular region of human tissue factor. Nature 370, 662-666 (1994) (Pubitemid 24270689)
15. Y. A. Muller, M. H. Ultsch, R. F. Kelley and A. M. de Vos: Structure of the extracellular domain of human tissue factor-Location of the factor VIIa binding site. Biochemistry 33, 10864-10870 (1994) (Pubitemid 24296338)
16. Y. A. Muller, M. H. Ultsch and A. M. de Vos: The crystal structure of the extracellular domain of human tissue factor refined to 1.7 angstrom resolution. J Mol Biol 256, 144-159 (1996)
17. M. Huang, R. Syed, E. A. Stura, M. J. Stone, R. S. Stefanko, W. Ruf, T. S. Edgington and I. A. Wilson: The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex. J Mol Biol 275, 873-894 (1998) (Pubitemid 28077702)
18. W. Ruf, A. Rehemtulla, J. H. Morrissey and T. S. Edgington: Phospholipid-independent and -dependent interactions required for tissue factor receptor and cofactor function. J Biol Chem 266, 2158-2166 (1991) (Pubitemid 21909043)
19. E. Waxman, J. B. A. Ross, T. M. Laue, A. Guha, S. V. Thiruvikraman, T. C. Lin, W. H. Konigsberg and Y. Nemerson: Tissue factor and its extracellular soluble domain-The relationship between intermolecular association with factor VIIa and enzymatic activity of the complex. Biochemistry 31, 3998-4003 (1992)
20. P. F. Neuenschwander and J. H. Morrissey: Deletion of the membrane anchoring region of tissue factor abolishes autoactivation of factor VII but not cofactor function. Analysis of a mutant with a selective deficiency in activity. J Biol Chem 267, 14477-14482 (1992)
21. S. Butenas, J. H. Lawson, M. Kalafatis and K. G. Mann: Cooperative interaction of divalent metal ions, substrate, and tissue factor with factor VIIa. Biochemistry 33, 3449-3456 (1994) (Pubitemid 24112660)
22. P. F. Neuenschwander and J. H. Morrissey: Roles of the membrane-interactive regions of factor VIIa and tissue factor. The factor VIIa Gla domain is dispensable for binding to tissue factor but important for activation of factor X. J Biol Chem 269, 8007-8013 (1994)
23. A. K. Sabharwal, J. J. Birktoft, J. Gorka, P. Wildgoose, L. C. Petersen and S. P. Bajaj: High affinity Ca(2+)-binding site in the serine protease domain of human factor VIIa and its role in tissue factor binding and development of catalytic activity. J Biol Chem 270, 15523-15530 (1995)
24. S. Higashi, N. Matsumoto and S. Iwanaga: Molecular mechanism of tissue factor-mediated acceleration of factor VIIa activity. J Biol Chem 271, 26569-26574 (1996) (Pubitemid 26359057)
25. C. D. Dickinson, C. R. Kelly, W. Ruf: Identification of surface residues mediating tissue factor binding and catalytic function of the serine protease factor VIIa. Proc Natl Acad Sci USA 93, 14379-14384 (1996) (Pubitemid 26418974)
26. R. Huber, R and W. Bode: Structural basis of the activation and action of trypsin. Acc Chem Res 11, 114-122 (1978)
27. K. D. Rand, T.J. Jørgensen, O. H. Olsen, E. Persson, O. N. Jensen, H. R. Stennicke and M. D. Andersen: Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange. J Biol Chem 281, 23018-23024 (2006)
28. S. P. Bajaj, A. E. Schmidt, S. Agah, M. S. Bajaj and K. Padmanabhan: High resolution structures of paminobenzamidine-and benzamidine-VIIa/soluble tissue factor: unpredicted conformation of the 192-193 peptide bond and mapping of Ca2+, Mg2+, Na+, and Zn2+ sites in factor VIIa. J Biol Chem 281, 24873-24888 (2006) (Pubitemid 44274259)
29. W. Ruf and C. D. Dickinson: Allosteric regulation of the cofactor-dependent serine protease coagulation factor VIIa. Trends Cardiovasc Med 8, 350-356 (1998) (Pubitemid 28565199)
30. A. W. Pike, A. M. Brzozowski, S. M. Roberts, O. H. Olsen and E. Persson: Structure of human factor VIIa and its implications for the triggering of blood coagulation. Proc Natl Acad Sci USA 96, 8925-8930 (1999) (Pubitemid 29374684)
31. G. Kemball-Cook, D. J. Johnson, E. G. Tuddeham and K. Harlos K: Crystal structure of active site-inhibited coagulation factor VIIa (des-Gla). J Struct Biol 127, 213-223 (1999)
32. R. J. Petrovan and W. Ruf W: Residue Met156 contributes to the labile enzyme conformation of coagulation factor VIIa. J Biol Chem 276, 6616-6620 (2001)
33. E. Persson, H. Bak, A. Østergaard and O. H. Olsen: Augmented intrinsic activity of Factor VIIa by replacement of residues 305, 314, 337 and 374: evidence of two unique mutational mechanisms of activity enhancement. Biochem J 379, 497-503 (2004) (Pubitemid 38570123)
34. E. Persson and O. H. Olsen: Allosteric activation of coagulation factor VIIa. Front Biosci 17, 3156-3163 (2011)
35. M. S. Bajaj, J. J. Birktoft, S. A. Steer and S. P. Bajaj: Structure and biology of tissue factor pathway inhibitor. Thromb Haemost 86, 959-972 (2001) (Pubitemid 32975818)
36. T. C. Wun, K. K. Kretzmer, T. J. Girard, J. P. Miletich and G. J. Broze Jr: Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. J Biol Chem 263, 6001-6004 (1988)
37. T. J. Girard, L. A. Warren, W. F. Novotny, K. M. Likert, S. G. Brown, J. P. Miletich and G. J. Broze Jr: Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor. Nature 338, 518-520 (1989) (Pubitemid 19107996)
38. R. J. Baugh, G. J. Broze Jr and S. Krishnaswamy: Regulation of extrinsic pathway factor Xa formation by tissue factor pathway inhibitor. J Biol Chem 273, 4378-4386 (1998) (Pubitemid 28103174)
39. S. P. Leytus, D. C. Foster, K. Kurachi and E. W. Davie: Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C. Biochemistry 25, 5098-5102 (1986) (Pubitemid 17016521)
40. S. Yoshitake, B. G. Schach, D. C. Foster, E. W. Davie and K. Kurachi: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry 24, 3736-3750 (1985) (Pubitemid 15011912)
41. D. W. Banner, A. D'Arcy, C. Chene, F. K. Winkler, A. Guha, W. H. Konigsberg, Y. Nemerson and D. Kirchhofer: The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature, 380, 41-46 (1996) (Pubitemid 26076234)
42. W. Ruf, J. R. Schullek, M. J. Stone and T. S. Edgington: Mutational mapping of functional residues in tissue factor: identification of factor VII recognition determinants in both structural modules of the predicted cytokine receptor homology domain. Biochemistry 33, 1565-1572 (1994) (Pubitemid 24093707)
43. J. R. Schullek, W. Ruf and T. S. Edgington: Key ligand interface residues in tissue factor contribute independently to factor VIIa binding. J Biol Chem 269, 19399-19403 (1994) (Pubitemid 24233463)
44. C. S. Gibbs, S. N. McCurdy, L. L. Leung and L. R. Paborsky: Identification of the factor VIIa binding site on tissue factor by homologous loop swap and alanine scanning mutagenesis. Biochemistry 33, 14003-14010 (1994) (Pubitemid 24382341)
45. W. Ruf, C. R. Kelly, J. R. Schullek, D. M. Martin, I. Polikarpov, C. W. Boys, E. G. Tuddenham and T. S. Edgington: Energetic contributions and topographical organization of ligand binding residues of tissue factor. Biochemistry 34, 6310-6315 (1995)
46. R. F. Kelley, K. E. Costas, M. P. O'Connell and R. A. Lazarus: Analysis of the factor VIIa binding site on human tissue factor: effects of tissue factor mutations on the kinetics and thermodynamics of binding. Biochemistry 34, 10383-10392 (1995)
47. J. R. Toomey, K. J. Smith and D. W. Stafford: Localization of the human tissue factor recognition determinant of human factor VIIa. J Biol Chem 266, 19198-19202 (1991) (Pubitemid 21908217)
48. B. J. Clarke, F. A. Ofosu, S. Sridhara, R. D. Bona, F. R. Rickles and M. A. Blajchman: The first epidermal growth factor domain of human coagulation factor VII is essential for binding with tissue factor. FEBS Lett 298, 206-210 (1992)
49. Y. Kazama, A. Pastuszyn, P. Wildgoose, T. Hamamoto and W. Kisiel: Isolation and characterization of proteolytic fragments of human factor VIIa which inhibit the tissue factor-enhanced amidolytic activity of factor VIIa. J Biol Chem 268, 16231-16240 (1993) (Pubitemid 23229920)
50. L. C. Petersen, J. Schiødt and U. Christensen: Involvement of the hydrophobic stack residues 39-44 of factor VIIa in tissue factor interactions. FEBS Lett 347, 73-79 (1994)
51. D. P. O'Brien, G. Kemball-Cook, A. M. Hutchinson, D. M. Martin, D. J. Johnson, P. G. Byfield, O. Takamiya, E. G. Tuddenham and J. H. McVey: Surface plasmon resonance studies of the interaction between factor VII and tissue factor. Demonstration of defective tissue factor binding in a variant FVII molecule (FVII-R79Q). Biochemistry 33, 14162-14169 (1994) (Pubitemid 24382361)
52. E. Persson: Influence of the gamma-carboxyglutamic acid-rich domain and hydrophobic stack of factor VIIa on tissue factor binding. Haemostasis 26, 31-34 (1996) (Pubitemid 26075716)
53. M. Soriano-Garcia, K. Padmanabhan, A. M. de Vos and A. Tulinsky: The Ca2+ ion and membrane binding structure of the Gla domain of Ca-prothrombin fragment 1. Biochemistry 31, 2554-2566 (1992)
54. C. R. Mosbaek, D. Nolan, E. Persson, D. I. Svergun, J. T. Bukrinsky and B. Vestergaard: Extensive small-angle Xray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility. Biochemistry 49, 9739-9745 (2010)
55. A. S. Minazzo, R. C. Darlington and J. B. Ross: Loop dynamics of the extracellular domain of human tissue factor and activation of factor VIIa. Biophys J 96, 681-692 (2009)
56. K. Vadivel, S. Agah, A.S. Messer, D. Cascio, M. S. Bajaj, S. Krishnaswamy, C.T. Esmon, K. Padmanabhan and S. P. Bajaj: Mg2+ is required for optimal folding of the γ-carboxyglutamic acid (Gla) domains of vitamin Kdependent clotting factors at physiological Ca2+. ASH Meeting 2011, abstract number 1172
57. V. Oganesyan, N. Oganesyan, S. Terzyan, D. Qu, Z. Dauter, N. L. Esmon and C.T. Esmon: The crystal structure of the endothelial protein C receptor and a bound phospholipid. J Biol Chem 277, 24851-24854 (2002) (Pubitemid 34951783)
58. Y. Shikamoto, T. Morita, Z. Fujimoto and H. Mizuno: Crystal structure of Mg2+-and Ca2+-bound Gla domain of factor IX complexed with binding protein. J Biol Chem 278, 24090-24094 (2003) (Pubitemid 36830242)
59. S. Agah and S. P. Bajaj: Role of magnesium in factor XIa catalyzed activation of factor IX: calcium binding to factor IX under physiologic magnesium. J Thromb Haemost 7, 1426-1428 (2009)
60. B. de Courcy, L. G. Pedersen, O. Parisel, N. Gresh, B. Silvi, J. Pilmé and J. P. Piquemal: Understanding selectivity of hard and soft metal cations within biological systems using the subvalence concept. I. Application to blood coagulation: direct cation-protein electronic effects vs. indirect interactions through water networks. J Chem Theory Comput 6, 1048-1063 (2010)
61. F. Sekiya, T. Yamashita, H. Atoda, Y. Komiyama and T. Morita: Regulation of the tertiary structure and function of coagulation factor IX by magnesium (II) ions. J Biol Chem 270, 14325-14331 (1995)
62. E. Persson and A. Ostergaard: Mg2+ binding to the Gla domain of factor X influences the interaction with tissue factor. J Thromb Haemost 5, 1977-1978 (2007) (Pubitemid 47288960)
63. B. Osterud, and S. I. Rapaport: Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci USA 74, 5260-5264 (1977)
64. Y. Nemerson: The Reaction between Bovine Brain Tissue Factor and Factors VII and X*. Biochemistry 5, 601-608 (1966)
65. G. Lu, G. J. Broze, Jr. and S. Krishnaswamy: Formation of factors IXa and Xa by the extrinsic pathway: differential regulation by tissue factor pathway inhibitor and antithrombin III. J Biol Chem 279, 17241-17249 (2004) (Pubitemid 38560482)
66. M. Ndonwi, G. J. Broze Jr, S. Agah, A. E. Schmidt and S. P. Bajaj. Substitution of the Gla domain in factor X with that of protein C impairs its interaction with factor VIIa/tissue factor: lack of comparable effect by similar substitution in factor IX. J Biol Chem 282, 15632-15644 (2007) (Pubitemid 47093274)
67. M. Ndonwi, G. J. Broze and S. P. Bajaj: The First Epidermal Growth Factor-like Domains of Factor Xa and IXa are Important for the Activation of the Factor VII-Tissue Factor Complex. J Thromb Haemost 1, 112-118 (2005) (Pubitemid 41647123)
68. F. Thiec, G. Cherel and O. D. Christophe: Role of the Gla and first epidermal growth factor-like domains of factor X in the prothrombinase and tissue factor-factor VIIa complexes. J Biol Chem 278, 10393-10399 (2003) (Pubitemid 36800304)
69. S. W. Chen, J. L. Pellequer, J. F. Schved and M. Giansily-Blaizot: Model of a ternary complex between activated factor VII, tissue factor and factor IX. Thromb Haemost 88, 74-82 (2002) (Pubitemid 34752270)
70. B. V. Norledge, R. J. Petrovan, W. Ruf and A. J. Olson: The tissue factor/factor VIIa/factor Xa complex: a model built by docking and site-directed mutagenesis. Proteins 53, 640-648 (2003) (Pubitemid 37352177)
71. D. Venkateswarlu, R. E. Duke, L. Perera, T. A. Darden and L. G. Pedersen: An all-atom solution-equilibrated model for human extrinsic blood coagulation complex (sTF-VIIa-Xa): a protein-protein docking and molecular dynamics refinement study. J Thromb Haemost 1, 2577-2588 (2003)
72. C. J. Lee, V. Chandrasekaran, S. Wu, R. E. Duke and L.G. Pedersen. Recent estimates of the structure of the factor VIIa (FVIIa)/tissue factor (TF) and factor Xa (FXa) ternary complex. Thromb Res 125, S7-S10 (2010)
73. J. G. Mandell, V. A. Roberts, M. E. Pique, V. Kotlovyi, J. C. Mitchell, E. Nelson, I. Tsigelny and L. F. Ten Eyck: Protein Docking Using Continuum Electrostatics and Geometric Fit. Prot Eng 14, 105-113 (2001). (Pubitemid 32397557)
74. B. Duncan and A. Olson: Applications of evolutionary programming for the prediction of protein-protein interactions. In: Evolutionary programming V: Proceedings of the 5th Annual Conference on Evolutionary Programming. Boston: MIT Press; 1996.
75. H.A. Gabb, R. M. Jackson and M. J. Sternberg: Modelling protein docking using shape complementarity, electrostatics and biochemical information. J Mol Biol 272, 106-120 (1997) (Pubitemid 27395541)
76. Z. Rao, P. Handford, M. Mayhew, V. Knott, G. G. Brownlee and D. Stuart: The structure of a Ca2+-binding epidermal growth factor-like domain: its role in proteinprotein interactions. Cell 82, 131-141 (1995)
77. K. Vadivel, A. Schmidt and S.P. Bajaj: Does protease domain of human factor ixa contain a sodium site? Evidence from the 1.64 angstrom resolution crystal structure. ASH Meeting 2011, abstract number 2246.
78. T. A. Jones, J-Y. Zou, S. W. Cowan and M. Kjeldgaard: Improved methods for the building of protein models in electron density maps and the location of errors in these models. Acta Cryst A47, 110-119 (1991)
79. B. R. Brooks, C. L. Brooks, 3rd, A. D. Mackerell, Jr., L. Nilsson, R. J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, A. Caflisch, L. Caves, Q. Cui, A. R. Dinner, M. Feig, S. Fischer, J. Gao, M. Hodoscek, W. Im, K. Kuczera, T. Lazaridis, J. Ma, V. Ovchinnikov, E. Paci, R. W. Pastor, C. B. Post, J. Z. Pu, M. Schaefer, B. Tidor, R. M. Venable, H. L. Woodcock, X. Wu, W. Yang, D. M. York and M. Karplus: CHARMM: the biomolecular simulation program. J Comp Chem 30, 1545-1614 (2009)
80. Q. Huang, P. F. Neuenschwander, A. R. Rezaie and J. H. Morrissey: Substrate recognition by tissue factor-factor VIIa. Evidence for interaction of residues Lys165 and Lys166 of tissue factor with the 4-carboxyglutamate-rich domain of factor X. J Biol Chem 271, 21752-21757 (1996) (Pubitemid 26303791)
81. D. Kirchhofer, M. T. Lipari, P. Moran, C. Eigenbrot and R. F. Kelley: The tissue factor region that interacts with substrates factor IX and Factor X. Biochemistry 39, 7380-7387 (2000) (Pubitemid 30422054)
82. D. Kirchhofer, C. Eigenbrot, M. T. Lipari, P. Moran, M. Peek and R. F. Kelley: The tissue factor region that interacts with factor Xa in the activation of factor VII. Biochemistry 40, 675-682 (2001) (Pubitemid 32096852)
83. C. Manithody, L. Yang and A. R. Rezaie: Identification of a basic region on tissue factor that interacts with the first epidermal growth factor-like domain of factor X. Biochemistry 46, 3193-3199 (2007) (Pubitemid 46449140)
84. W. Ruf, J. Shobe, S. M. Rao, C. D. Dickinson, A. Olson and T. S. Edgington: Importance of factor VIIa Gladomain residue Arg-36 for recognition of the macromolecular substrate factor X Gla-domain. Biochemistry 38, 1957-1966 (1999)
85. D. Zhong, K. J. Smith, J. J. Birktoft and S. P. Bajaj: First epidermal growth factor-like domain of human blood coagulation factor IX is required for its activation by factor VIIa/tissue factor but not by factor XIa. Proc Natl Acad Sci USA 91, 3574-3578 (1994) (Pubitemid 24139472)
86. D. Zhong, M. S. Bajaj, A. E. Schmidt and S. P. Bajaj: The N-terminal epidermal growth factor-like domain in factor IX and factor X represents an important recognition motif for binding to tissue factor. J Biol Chem 277, 3622-31 (2002) (Pubitemid 34953235)
87. W. Ruf: Factor VIIa residue Arg290 is required for efficient activation of the macromolecular substrate factor X. Biochemistry 33, 11631-6 (1994) (Pubitemid 24330097)
88. E. Persson, L. S. Nielsen and O. H. Olsen: Substitution of aspartic acid for methionine-306 in factor VIIa abolishes the allosteric linkage between the active site and the binding interface with tissue factor. Biochemistry 40, 3251-3256 (2001) (Pubitemid 32221625)
89. F. S. Kittur, C. Manithody, J. H. Morrissey and A. R. Rezaie: The cofactor function of the N-terminal domain of tissue factor. J Biol Chem 279, 39745-39749 (2004) (Pubitemid 39258243)
90. S. P. Bajaj and J. J. Birktoft: Human factor IX and factor IXa. Methods in Enzymology 222, 96-128 (1993) (Pubitemid 23303230)
91. E. Di Cera, E. R. Guinto, A. Vindigni, Q. D. Dang, Y. M. Ayala, M. Wuyi and A. Tulinsky: The Na+ binding site of thrombin. J Biol Chem 270, 22089-22092 (1995)
92. 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, 37863-37870 (2002)
93. 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, 78-91 (2005) (Pubitemid 40804733)
94. A.E. Schmidt: Allostery in Serine proteases. Ph.D thesis, St. Louis University (2005)
95. K. Gopalakrishna and A. R. Rezaie: The influence of sodium ion binding on factor IXa activity. Thromb Haemost 95, 936-941 (2006) (Pubitemid 43933750)
96. L. C. Petersen, O. H. Olsen, L. S. Nielsen, P. O. Freskgård and E. Persson: Binding of Zn2+ to a Ca2+ loop allosterically attenuates the activity of factor VIIa and reduces its affinity for tissue factor. Protein Sci 9, 859-866 (2000) (Pubitemid 30353327)
97. A. H. Pedersen, T. Lund-Hansen, Y. Komiyama, L. C. Petersen, P. B. Oestergård and W. Kisiel: Inhibition of recombinant human blood coagulation factor VIIa amidolytic and proteolytic activity by zinc ions. Thromb Haemost 65, 528-534 (1991)
98. J. J. Perona and C. S. Craik: Structural basis of substrate specificity in the serine proteases. Protein Sci 4, 337-360 (1995)
99. H. P. Hopfner, A. Lang, A. Karcher, K. Sichler, E. Kopetzki, H. Brandstetter, R. Huber, W. Bode and R. A. Engh: Coagulation factor IXa: the relaxed conformation of Tyr99 blocks substrate binding. Structure 7, 989-996 (1999) (Pubitemid 29372520)
100. O. Klingler, H. Matter, M. Schudok, S. P. Bajaj, J. Czech, M. Lorenz, H. P. Nestler, H. Schreuder and P. Wildgoose: Design, synthesis, and structure-activity relationship of a new class of amidinophenylurea-based factor VIIa inhibitors. Bioorg Med Chem Lett 13, 1463-1437 (2003)
101. A.G. Olivero, C. Eigenbrot, R. Goldsmith, K. Robarge, D. R. Artis, J. Flygare, T. Rawson, D.P. Sutherlin, S. Kadkhodayan, M. Beresini, L. O. Elliott, G. G. DeGuzman, D. W. Banner, M. Ultsch, U. Marzec, S. R. Hanson, C. Refino, S. Bunting and D. Kirchhofer: A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo. J Biol Chem 280, 9160-9169 (2005) (Pubitemid 41818227)
102. K. G. Zbinden, U. Obst-Sander, K. Hilpert, H. Kühne, D. W. Banner, H. J. Böhm, J. Stahl M, Ackermann, L. Alig, L. Weber, H. P. Wessel, M. A. Riederer, T. B. Tschopp and T. Lavé: Selective and orally bioavailable phenylglycine tissue factor/factor VIIa inhibitors. Bioorg Med Chem Lett 15, 5344-5352 (2005) (Pubitemid 41463678)
103. E. Zhang, R. St Charles, and A. Tulinsky: Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant. J Mol Biol 285, 2089-2104 (1999) (Pubitemid 29078173)
104. K. Sichler, D. W. Banner, A. D'Arcy, K. P. Hopfner, R. Huber, W. Bode, G. B. Kresse, E. Kopetzki and H. Brandstetter: Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions. J Mol Biol 322, 591-603 (2002)
105. S. Krishnaswamy: Exosite-driven substrate specificity and function in coagulation. J Thromb Haemost 3, 54-67 (2005) (Pubitemid 41647115)
106. M. J. Burgering, L. P. Orbons, A. van der Doelen, J. Mulders, H. J. Theunissen, P. D. Grootenhuis, W. Bode, R. Huber and M. T. Stubbs: The second Kunitz domain of human tissue factor pathway inhibitor: cloning, structure determination and interaction with factor Xa. J Mol Biol 269, 395-407 (1997) (Pubitemid 27267761)
107. K. Carlsson, P. O. Freskgård, E. Persson, U. Carlsson and M. Svensson: Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factorfactor VIIa-factor Xa-tissue factor pathway inhibitor. Eur J Biochem 270, 2576-2582 (2003) (Pubitemid 36723987)
108. I. Schechter and A. Berger: On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun. 27, 157-162 (1967)