The story of the serpin plasminogen activator inhibitor I: Is there any need for another mutant?

Thrombosis and Haemostasis

Volumn 92, Issue 5, 2004, Pages 898-924

  De Taeye, Bart ^a   Gils, Ann ^a   Declerck, Paul J ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Mutagenesis; PAI I; Review; Serpin; Structure function

Indexed keywords

ALPHA 2 MACROGLOBULIN; ANTHRANILIC ACID DERIVATIVE; COMPLEMENTARY DNA; CYSTEINE; FIBRIN; HEPARIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; PLASMIN; PLASMINOGEN; PLASMINOGEN ACTIVATOR; PLASMINOGEN ACTIVATOR INHIBITOR 1; SERINE PROTEINASE INHIBITOR; TRYPTOPHAN; UROKINASE; UROKINASE RECEPTOR; VERY LOW DENSITY LIPOPROTEIN RECEPTOR; VITRONECTIN;

AMINO ACID SUBSTITUTION; ATHEROSCLEROSIS; BETA SHEET; BINDING SITE; CARDIOVASCULAR DISEASE; CELL MIGRATION; COMPLEX FORMATION; DIABETES MELLITUS; ENZYME INHIBITION; GENE MUTATION; GENETIC VARIABILITY; HUMAN; HYPERTENSION; MOLECULAR CLONING; MUTAGENESIS; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN GLYCOSYLATION; PROTEIN POLYMERIZATION; PROTEIN STABILITY; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; STRUCTURE ACTIVITY RELATION; TISSUE REGENERATION;

ANIMALS; HUMANS; MUTATION; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN BINDING; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; VARIATION (GENETICS);

EID: 9144257322     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH04-05-0269     Document Type: Review

References (170)

1. Andreasen PA, Nielsen LS, Kristensen P, et al. Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinase-type plasminogen activator, but not its proenzyme. J Biol Chem 1986; 261: 7644-51.
2. Ginsburg D, Zeheb R, Yang AY, et al. cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest 1986; 78: 1673-80.
3. Ny T, Sawdey M, Lawrence D, et al. Cloning and sequence of a cDNA coding for the human beta- migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci U S A 1986; 83: 6776-80.
4. Pannekoek H, Veerman H, Lambers H, et al. Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family. EMBO J 1986; 5: 2539-44.
5. 1,-Antitrypsin and the serpins: variation and countervariation. TIBS 1985; 1: 20-24.
6. Travis J, Salvesen GS. Human plasma proteinase inhibitors. Annu Rev Biochem 1983; 52: 655-709.
7. Carrell RW, Boswell DR. Serpins: the superfamily of plasma serine proteinase inhibitors. In: Barrett, Salvesen, editors. Proteinase inhibitors. Elsevier Science, 1986: 403-20.
8. Huber R, Carrell RW. Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins. Biochemistry 1989; 28: 8951-66.
9. Schechter I, Berger A. On the size of the active site in proteases. Biochem Biophys Res Commun 1967; 27: 157-62.
10. Gils A, Declerck PJ. Structure-function relationship in serpins: current concepts and controversies. Thromb Haemost 1998; 80: 531-41.
11. Laskowski M, Jr., Kato I. Protein inhibitors of proteinases. Annu Rev Biochem 1980; 49: 593-626.
12. Egelund R, Rodenburg KW, Andreasen PA, et al. An ester bond linking a fragment of a serine proteinase to its serpin inhibitor. Biochemistry 1998; 37: 6375-9.
13. Lawrence DA, Ginsburg D, Day DE, et al. Serpin-protease complexes are trapped as stable acyl-enzyme intermediates. J Biol Chem 1995; 270: 25309-12.
14. Lindahl TL, Ohlsson PI, Wiman B. The mechanism of the reaction between human plasminogen- activator inhibitor 1 and tissue plasminogen activator. Biochem J 1990; 265: 109-13.
15. Wilczynska M, Fa M, Ohlsson PI, et al. The inhibition mechanism of serpins. Evidence that the mobile reactive center loop is cleaved in the native protease-inhibitor complex. J Biol Chem 1995; 270: 29652-5.
16. Gettins PGW, Patston PA, Olson ST. Serpins: structure, function and biology. Heidelberg: Springer-Verlag, 1996.
17. Declerck PJ, De Mol M, Vaughan DE, et al. Identification of a conformationally distinct form of plasminogen activator inhibitor-1, acting as a noninhibitory substrate for tissue-type plasminogen activator. J Biol Chem 1992; 267: 11693-6.
18. Gils A, Declerck PJ. Proteinase specificity and functional diversity in point mutants of plasminogen activator inhibitor 1. J Biol Chem 1997; 272: 12662-6.
19. Sharp AM, Stein PE, Pannu NS, et al. The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion. Structure 1999; 7: 111-18.
20. Nar H, Bauer M, Stassen JM, et al. Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation. J Mol Biol 2000; 297: 683-95.
21. Hekman CM, Loskutoff DJ. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 1985; 260: 11581-7.
22. Mottonen J, Strand A, Symersky J, et al. Structural basis of latency in plasminogen activator inhibitor-1. Nature 1992; 355: 270-3.
23. Carrell RW, Stein PE, Fermi G, Wardell MR. Biological implications of a 3 A structure of dimeric antithrombin. Structure 1994; 2: 257-70.
24. Urano T, Strandberg L, Johansson LB, et al. A substrate-like form of plasminogen-activator-inhibitor type 1. Conversions between different forms by sodium dodecyl sulphate. Eur J Biochem 1992; 209: 985-92.
25. Munch M, Heegaard CW, Andreasen PA. Interconversions between active, inert and substrate forms of denatured/refolded type-1 plasminogen activator inhibitor. Biochim Biophys Acta 1993; 1202: 29-37.
26. Aertgeerts K, De Bondt HL, De Ranter CJ, et al. Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1. Nat Struct Biol 1995; 2: 891-7.
27. Carrell RW, Stein PE. The biostructural pathology of the serpins: critical function of sheet opening mechanism. Biol Chem Hoppe Seyler 1996; 377: 1-17.
28. Binder BR, Christ G, Gruber F, et al. Plasminogen activator inhibitor 1: physiological and pathophysiological roles. News Physiol Sci 2002; 17: 56-61.
29. Gils A, Declerck PJ. The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors. Thromb Haemost 2004; 91: 425-37.
30. Durand MK, Bodker JS, Christensen A, et al. Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis. Thromb Haemost 2004; 91: 438-49.
31. Manchanda N, Schwartz BS. Interaction of single-chain urokinase and plasminogen activator inhibitor type 1. J Biol Chem 1995; 270: 20032-5.
32. Behrendt N, List K, Andreasen PA, et al. The pro-urokinase plasminogen-activation system in the presence of serpin-type inhibitors and the urokinase receptor: rescue of activity through reciprocal pro-enzyme activation. Biochem J 2003; 371: 277-87.
33. Keijer J, Linders M, Wegman JJ, et al. On the target specificity of plasminogen activator inhibitor 1: the role of heparin, vitronectin, and the reactive site. Blood 1991; 78: 1254-61.
34. Hekman CM, Loskutoff DJ. Bovine plasminogen activator inhibitor 1: specificity determinations and comparison of the active, latent, and guanidine-activated forms. Biochemistry 1988; 27: 2911-18.
35. Sherman PM, Lawrence DA, Yang AY, et al. Saturation mutagenesis of the plasminogen activator inhibitor-1 reactive center. J Biol Chem 1992; 267: 7588-95.
36. Sherman PM, Lawrence DA, Verhamme IM, et al. Identification of tissue-type plasminogen activator-specific plasminogen activator inhibitor-1 mutants. Evidence that second sites of interaction contribute to target specificity. J Biol Chem 1995; 270: 9301-6.
37. Shubeita HE, Cottey TL, Franke AE, et al. Mutational and immunochemical analysis of plasminogen activator inhibitor 1. J Biol Chem 1990; 265: 18379-85.
38. Keijer J, Ehrlich HJ, Linders M, et al. Vitronectin governs the interaction between plasminogen activator inhibitor 1 and tissue-type plasminogen activator. J Biol Chem 1991; 266: 10700-7.
39. Stefansson S, Yepes M, Gorlatova N, et al. Mutants of plasminogen activator inhibitor-1 designed to inhibit Neutrophil Elastase and Cathepsin G are more effective in vivo than their endogenous inhibitors. J Biol Chem 2004; 279: 29981-7.
40. Ehrlich AJ, Gebbink RK, Keijer J, et al. Alteration of serpin specificity by a protein cofactor. Vitronectin endows plasminogen activator inhibitor 1 with thrombin inhibitory properties. J Biol Chem 1990; 265: 13029-35.
41. Madison EL, Goldsmith EJ, Gething MJ, et al. Restoration of serine protease-inhibitor interaction by protein engineering. J Biol Chem 1990; 265: 21423-6.
42. Audenaert AM, Knockaert I, Collen D, et al. Conversion of plasminogen activator inhibitor-1 from inhibitor to substrate by point mutations in the reactive-site loop. J Biol Chem 1994; 269: 19559-64.
43. Tucker HM, Gerard RD. Sequence requirements in the reactive-center loop of plasminogen-activator inhibitor-1 for recognition of plasminogen activators. Eur J Biochem 1996; 237: 180-7.
44. van Meijer M, Roelofs Y, Neels J, et al. Selective screening of a large phage display library of plasminogen activator inhibitor 1 mutants to localize interaction sites with either thrombin or the variable region 1 of tissue- type plasminogen activator. J Biol Chem 1996; 271: 7423-8.
45. Wang Q, Shaltiel S. Distal hinge of plasminogen activator inhibitor-1 involves its latency transition and specificities toward serine proteases. BMC Biochemistry 2003; 4.
46. Chmielewska J, Ranby M, Wiman B. Kinetics of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Evidence for 'second-site' interactions. Biochem J 1988; 251: 327-32.
47. Lawrence DA, Strandberg L, Ericson J, et al. Structure-function studies of the SERPIN plasminogen activator inhibitor type 1. Analysis of chimeric strained loop mutants. J Biol Chem 1990; 265: 20293-301.
48. Madison EL, Goldsmith EJ, Gerard RD, et al. Serpin-resistant mutants of human tissue-type plasminogen activator. Nature 1989; 339: 721-4.
49. Bottomley SP, Lawrenson ID, Tew D, et al. The role of strand 1 of the C beta-sheet in the structure and function of alpha(1)-antitrypsin. Protein Sci 2001; 10: 2518-24.
50. Ibarra CA, Blouse GE, Christian TD, et al. The contribution of the exosite residues of plasminogen activator inhibitor-1 to proteinase inhibition. J Biol Chem 2004; 279: 3643-50.
51. Sun J, Whisstock JC, Harriott P, et al. Importance of the P4 'residue in human granzyme B inhibitors and substrates revealed by scanning mutagenesis of the proteinase inhibitor 9 reactive center loop. J Biol Chem 2001; 276: 15177-84.
52. Lawrence DA, Ginsburg D, Day DE, et al. Serpin-protease complexes are trapped as stable acyl-enzyme intermediates. J Biol Chem 1995; 270: 25309-12.
53. Huntington JA, Read RJ, Carrell RW. Structure of a serpin-protease complex shows inhibition by deformation. Nature 2000; 407: 923-6.
54. Gils A, Knockaert I, Declerck PJ. Construction and characterization of plasminogen activator inhibitor-1 mutants in which part of the active site loop is deleted. Fibrinolysis 1997; 11: 265-71.
55. Zhou A, Carrell RW, Huntington JA. The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop. J Biol Chem 2001; 276: 27541-7.
56. De Taeye B, Verbeke K, Compernolle G, et al. Structural determinants in the stability of the serpin/proteinase complex. Biochem Biophys Res Commun 2003; 307: 529-34.
57. De Taeye B, Compernolle G, Declerck PJ. Site-directed targeting of plasminogen activator inhibitor-1 as an example for a novel approach in rational drug design. J Biol Chem 2004; 279: 20447-50.
58. Naessens D, Gils A, Compernolle G, et al. Elucidation of a novel epitope of a substrate-inducing monoclonal antibody against the serpin PAI-1. J Thromb Haemost 2003; 1: 1028-33.
59. Komissarov AA, Declerck PJ, Shore JD. Mechanisms of Conversion of plasminogen activator inhibitor 1 from a suicide inhibitor to a substrate by monoclonal antibodies. J Biol Chem 2002; 277: 43858-65.
60. Sui GC, Wiman B. The Bb-sheet in the PAI-1 molecule plays an important role for its stability. Thromb Haemost 2000; 83: 896-901.
61. Tucker HM, Mottonen J, Goldsmith EJ, et al. Engineering of plasminogen activator inhibitor-1 to reduce the rate of latency transition [letter]. Nat Struct Biol 1995; 2: 442-5.
62. Bjorquist P, Ehnebom J, Inghardt T, et al. Identification of the binding site for a low-molecular-weight inhibitor of plasminogen activator inhibitor type 1 by site- directed mutagenesis. Biochemistry 1998; 37: 1227-34.
63. Gils A, Vleugels N, Tobback K, et al. Characterization of plasminogen activator inhibitor 1 mutants containing the p13 to p10 region of ovalbumin or antithrombin iii: evidence that the p13 residue contributes significantly to the active to substrate transition. Biochim Biophys Acta 1998; 1387: 291-7.
64. Lawrence DA, Olson ST, Muhammad S, et al. Partitioning of serpin-proteinase reactions between stable inhibition and substrate cleavage is regulated by the rate of serpin reactive center loop insertion into beta-sheet A. J Biol Chem 2000; 275: 5839-44.
65. Devraj Kizuk R, Chui DH, Prochownik EV, et al. Antithrombin-III-Hamilton: a gene with a point mutation (guanine to adenine) in codon 382 causing impaired serine protease reactivity. Blood 1988; 72: 1518-23.
66. Perry DJ, Harper PL, Fairham S, et al. Antithrombin Cambridge, 384 Ala to Pro: a new variant identified using the polymerase chain reaction. FEBS Lett 1989; 254: 174-6.
67. Stein PE, Leslie AG, Finch JT, et al. Crystal structure of ovalbumin as a model for the reactive centre of serpins. Nature 1990; 347: 99-102.
68. Carrell RW, Evans DL, Stein PE. Mobile reactive centre of serpins and the control of thrombosis. Nature 1991; 353: 576-8.
69. Stein P, Chothia C. Serpin tertiary structure transformation. J Mol Biol 1991; 221: 615-21.
70. Skriver K, Wikoff WR, Patston PA, et al. Substrate properties of C1 inhibitor Ma (alanine 434 - glutamic acid). Genetic and structural evidence suggesting that the P12- region contains critical determinants of serine protease inhibitor/substrate status. J Biol Chem 1991; 266: 9216-21.
71. Gils A, Knockaert I, Declerck PJ. Substrate behavior of plasminogen activator inhibitor-1 is not associated with a lack of insertion of the reactive site loop. Biochemistry 1996; 35: 7474-81.
72. Lawrence DA, Olson ST, Palaniappan S, et al. Serpin reactive center loop mobility is required for inhibitor function but not for enzyme recognition. J Biol Chem 1994; 269: 27657-62.
73. Patston PA, Gettins P, Beechem J, et al. Mechanism of serpin action: evidence that C1 inhibitor functions as a suicide substrate. Biochemistry 1991; 30: 8876-82.
74. Stavridi ES, O'Malley K, Lukacs CM, et al. Structural change in alpha-chymotrypsin induced by complexation with alpha 1-antichymotrypsin as seen by enhanced sensitivity to proteolysis. Biochemistry 1996; 35: 10608-15.
75. Schechter NM, Jordan LM, James AM, et al. Reaction of human chymase with reactive site variants of alpha 1- antichymotrypsin odulation of inhibitor versus substrate properties. J Biol Chem 1993; 268: 23626-33.
76. Olson ST. Heparin and ionic strength-dependent conversion of antithrombin III from an inhibitor to a substrate of alpha-thrombin. J Biol Chem 1985; 260: 10153-60.
77. De Taeye B, Compernolle G, Dewilde M, et al. Immobilization of the distal hinge in the labile serpin plasminogen activator inhibitor 1: Identification of a transition state with distinct conformational and functional properties. J Biol Chem 2003; 278: 23899-905.
78. Hagglof P, Bergstrom F, Wilczynska M, et al. The reactive-center loop of active PAI-1 is folded close to the protein core and can be partially inserted. J Mol Biol 2004; 335: 823-32.
79. Olson ST, Swanson R, Day D, et al. Resolution of Michaelis complex, acylation, and conformational change steps in the reactions of the serpin, plasminogen activator inhibitor-1, with tissue plasminogen activator and trypsin. Biochemistry 2001; 40: 11742-56.
80. Lindahl TL, Sigurdardottir O, Wiman B. Stability of plasminogen activator inhibitor 1 (PAI-1). Thromb Haemost 1989; 62: 748-51.
81. Sancho E, Tonge DW, Hockney RC, et al. Purification and characterization of active and stable recombinant plasminogen-activator inhibitor accumulated at high levels in Escherichia coli. Eur J Biochem 1994; 224: 125-34.
82. Keijer J, Linders M, Ehrlich HJ, et al. Stabilization of plasminogen activator inhibitor 1 (PAI-1) activity by arginine: possible implications for the interaction of PAI-1 with vitronectin. Fibrinolysis 1990; 4: 153-9.
83. Mangs H, Sui GC, Wiman B. PAI-1 stability: the role of histidine residues. FEBS Lett 2000; 475: 192-6.
84. Kvassman JO, Lawrence DA, Shore JD. The acid stabilization of plasminogen activator inhibitor-1 depends on protonation of a single group that affects loop insertion into beta-sheet A. J Biol Chem 1995; 270: 27942-7.
85. Sui GC, Mangs H, Wiman B. The role of His(143) for the pH-dependent stability of plasminogen activator inhibitor-1. Biochim Biophys Acta 1999; 1434: 58-63.
86. 221. FEBS Lett 1998; 423: 319-23.
87. Lawrence DA, Loskutoff DJ. Inactivation of plasminogen activator inhibitor by oxidants. Biochemistry 1986; 25: 6351-5.
88. Strandberg L, Lawrence DA, Johansson LB, et al. The oxidative inactivation of plasminogen activator inhibitor type 1 results from a conformational change in the molecule and does not require the involvement of the P1' methionine. J Biol Chem 1991; 266: 13852-8.
89. Berkenpas MB, Lawrence DA, Ginsburg D. Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBO J 1995; 14: 2969-77.
90. Vleugels N, Leys J, Knockaert I, et al. Effect of stabilizing versus destabilizing interactions on plasminogen activator inhibitor-1. Thromb Haemost 2000; 84: 871-5.
91. Stoop AA, Eldering E, Dafforn TR, et al. Different structural requirements for plasminogen activator inhibitor 1 (PAI-1) during latency transition and proteinase inhibition as evidenced by phage-displayed hypermutated PAI-1 libraries. J Mol Biol 2001; 305: 773-83.
92. Kruger P, Verheyden S, Declerck PJ, et al. Extending the capabilities of targeted molecular dynamics: simulation of a large conformational transition in plasminogen activator inhibitor 1. Protein Sci 2001; 10: 798-808.
93. Shore JD, Day DE, Francis Chmura AM, et al. A fluorescent probe study of plasminogen activator inhibitor-1. Evidence for reactive center loop insertion and its role in the inhibitory mechanism. J Biol Chem 1995; 270: 5395-8.
94. Lawrence DA, Olson ST, Palaniappan S, et al. Engineering plasminogen activator inhibitor 1 mutants with increased functional stability. Biochemistry 1994; 33: 3643-8.
95. Chorostowska-Wynimko J, Swiercz R, Skrzypczak-Jankun E, et al. A novel form of the plasminogen activator inhibitor created by cysteine mutations extends its half-life: relevance to cancer and angiogenesis. Mol Cancer Ther 2003; 2: 19-28.
96. Hansen M, Busse MN, Andreasen PA. Importance of the amino-acid composition of the shutter region of plasminogen activator inhibitor-1 for its transitions to latent and substrate forms. Eur J Biochem 2001; 268: 6274-83.
97. Kirkegaard T, Jensen S, Schousboe SL, et al. Engineering of conformations of plasminogen activator inhibitor-1 - A crucial role of beta-strand 5A residues in the transition of active form to latent and substrate forms. Eur J Biochem 1999; 263: 577-86.
98. Wind T, Jensen JK, Dupont DM, et al. Mutational analysis of plasminogen activator inhibitor-1. Eur J Biochem 2003; 270: 1680-8.
99. Engh RA, Schulze AJ, Huber R, et al. Serpin structures. Behring Inst Mitt 1993; 41-62.
100. Gils A, Lu J, Aertgeerts K, et al. Identification of positively charged residues contributing to the stability of plasminogen activator inhibitor 1. FEBS Lett 1997; 415: 192-5.
101. Sui GC, Wiman B. Functional effects of single amino acid substitutions in the region of phe(113) to asp(138) in the plasminogen activator inhibitor 1 molecule. Biochem J 1998; 331: 409-15.
102. Irving JA, Pike RN, Lesk AM, et al. Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function. Genome Res 2000; 10: 1845-64.
103. Declerck PJ, De Mol M, Alessi MC, et al. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). J Biol Chem 1988; 263: 15454-61.
104. Naski MC, Lawrence DA, Mosher DF, et al. Kinetics of inactivation of alpha-thrombin by plasminogen activator inhibitor-1. Comparison of the effects of native and urea-treated forms of vitronectin. J Biol Chem 1993; 268: 12367-72.
105. Lawrence DA, Palaniappan S, Stefansson S, et al. Characterization of the binding of different conformational forms of plasminogen activator inhibitor 1 to vitronectin: implications for the regulation of pericellular proteolysis. J Biol Chem 1997; 272: 7676-80.
106. Keijer J, Linders M, van Zonneveld AJ, et al. The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: localization of interaction sites and physiologic relevance. Blood 1991; 78: 401-9.
107. Ehrlich HJ, Gebbink RK, Keijer J, et al. Elucidation of structural requirements on plasminogen activator inhibitor 1 for binding to heparin. J Biol Chem 1992; 267: 11606-11.
108. Fa M, Karolin J, Aleshkov S, et al. Time-resolved polarized fluorescence spectroscopy studies of plasminogen activator inhibitor type 1: conformational changes of the reactive center upon interactions with target proteases, vitronectin and heparin. Biochemistry 1995; 34: 13833-40.
109. Gibson A, Baburaj K, Day DE, et al. The use of fluorescent probes to characterize conformational changes in the interaction between vitronectin and plasminogen activator inhibitor-1. J Biol Chem 1997; 272: 5112-21.
110. Fa M, Bergstrom F, Karolin J, et al. Conformational studies of plasminogen activator inhibitor type 1 by fluorescence spectroscopy. Analysis of the reactive centre of inhibitory and substrate forms, and their respective reactive-centre cleaved forms. Eur J Biochem 2000; 267: 3729-34.
111. van Meijer M, Gebbink RK, Preissner KT, et al. Determination of the vitronectin binding site on plasminogen activator inhibitor 1 (PAI-1). FEBS Lett 1994; 352: 342-6.
112. Padmanabhan J, Sane DC. Localization of a vitronectin binding region of plasminogen activator inhibitor-1. Thromb Haemost 1995; 73: 829-34.
113. Lawrence DA, Berkenpas MB, Palaniappan S, et al. Localization of vitronectin binding domain in plasminogen activator inhibitor-1. J Biol Chem 1994; 269: 15223-8.
114. Arroyo DP, Schroeck F, Sinner EK, et al. Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin. Eur J Biochem 2002; 269: 184-92.
115. Jensen JK, Wind T, Andreasen PA. The vitronectin binding area of plasminogen activator inhibitor-1, mapped by mutagenesis and protection against an inactivating organochemical ligand. FEBS Lett 2002; 521: 91-4.
116. Jensen JK, Durand KV, Skeldal S, et al. Construction of a plasminogen activator inhibitor-1 variant without measurable affinity to vitronectin but otherwise normal. FEBS Lett 2004; 556: 175-9.
117. Im H, Yu MH. Role of Lys335 in the metastability and function of inhibitory serpins. Protein Sci 2000; 9: 934-41.
118. Zhou A, Huntington JA, Pannu NS, et al. How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration. Nat Struct Biol 2003; 10: 541-4.
119. Mayasundari A, Whittemore NA, Serpersu EH, et al. The solution structure of the N-terminal domain of human vitronectin. J Biol Chem 2004; 279: 29359-66.
120. Kamikubo Y, De Guzman R, Kroon G, et al. Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin. Biochemistry 2004; 43: 6519-34.
121. Ehrlich HJ, Keijer J, Preissner KT, et al. Functional interaction of plasminogen activator inhibitor type 1 (PAI- 1) and heparin. Biochemistry 1991; 30: 1021-8.
122. Stringer HA, Pannekoek H. The significance of fibrin binding by plasminogen activator inhibitor 1 for the mechanism of tissue-type plasminogen activator-mediated fibrinolysis. J Biol Chem 1995; 270: 11205-8.
123. Podor TJ, Peterson CB, Lawrence DA, et al. Type 1 plasminogen activator inhibitor binds to fibrin via vitronectin. J Biol Chem 2000; 275: 19788-94.
124. Andreasen PA, Sottrup Jensen L, Kjoller L, et al. Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes. FEBS Lett 1994; 338: 239-45.
125. Andreasen PA, Kjoller L, Christensen L, et al. The urokinase type plasminogen activator system in cancer metastasis: a review. Int J Cancer 1997; 72: 1-22.
126. Horn IR, van den Berg BM, van der Meijden PZ, et al. Molecular analysis of ligand binding to the second cluster of complement-type repeats of the low density lipoprotein receptor- related protein. Evidence for an allosteric component in receptor- associated protein-mediated inhibition of ligand binding. J Biol Chem 1997; 272: 13608-13.
127. Nykjaer A, Petersen CM, Moller B, et al. Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes. J Biol Chem 1992; 267: 14543-6.
128. Nykjaer A, Kjoller L, Cohen RL, et al. Regions involved in binding of urokinase-type-1 inhibitor complex and pro-urokinase to the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that the urokinase receptor protects pro-urokinase against binding to the endocytic receptor. J Biol Chem 1994; 269: 25668-76.
129. Rodenburg KW, Kjoller L, Petersen HH, et al. Binding of urokinase-type plasminogen activator plasminogen activator inhibitor-1 complex to the endocytosis receptors alpha(2)-macroglobulin receptor low-density lipoprotein receptor- related protein and very-low-density lipoprotein receptor involves basic residues in the inhibitor. Biocheml J 1998; 329: 55-63.
130. Horn IR, van den Berg BM, Moestrup SK, et al. Plasminogen activator inhibitor 1 contains a cryptic high affinity receptor binding site that is exposed upon complex formation with tissue-type plasminogen activator. Thromb Haemost 1998; 80: 822-8.
131. Stefansson S, Muhammad S, Cheng XF, et al. Plasminogen activator inhibitor-1 contains a cryptic high affinity binding site for the low density lipoprotein receptor- related protein. J Biol Chem 1998; 273: 6358-66.
132. Gils A, Pedersen KE, Skottrup P, et al. Biochemical importance of glycosylation of plasminogen activator inhibitor-1. Thromb Haemost 2003; 90: 206-17.
133. Lawrence D, Strandberg L, Grundstrom T, et al. Purification of active human plasminogen activator inhibitor 1 from Escherichia coli. Comparison with natural and recombinant forms purified from eucaryotic cells. Eur J Biochem 1989; 186: 523-33.
134. Gils A, Knockaert I, Brouwers E, et al. Glycosylation dependent conformational transitions in plasminogen activator inhibitor-1: evidence for the presence of two active conformations. Fibrinolysis 2000; 14: 58-64.
135. Andreasen PA, Egelund R, Jensen S, et al. Solvent effects on activity and conformation of plasminogen activator inhibitor-1. Thromb Haemost 1999; 81: 407-14.
136. Lomas DA, Carrell RW. Serpinopathies and the conformational dementias. Nature Reviews Genetics 2002; 3: 759-68.
137. Jin L, Abrahams JP, Skinner R, et al. The anticoagulant activation of antithrombin by heparin. Proc Natl Acad Sci USA 1997; 94: 14683-8.
138. Schreuder HA, de Boer B, Dijkema R, et al. The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions. Nat Struct Biol 1994; 1: 48-54.
139. Stout TJ, Graham H, Buckley DI, et al. Structures of active and latent PAI-1: a possible stabilizing role for chloride ions. Biochemistry 2000; 39: 8460-9.
140. Lomas DA, Evans DL, Finch JT, et al. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 1992; 357: 605-7.
141. Egelund R, Einholm AP, Pedersen KE, et al. A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands - Ligand-induced serpin polymerization. J Biol Chem 2001; 276: 13077-86.
142. Pedersen KE, Einholm AP, Christensen A, et al. Plasminogen activator inhibitor-1 polymers, induced by inactivating amphipathic organochemical ligands. Biochem J 2003; 372: 747-55.
143. Zhou A, Faint R, Charlton P, et al. Polymerization of plasminogen activator inhibitor-1. J Biol Chem 2001; 276: 9115-22.
144. Blouse GE, Perron MJ, Thompson JH, et al. A concerted structural transition in the plasminogen activator inhibitor-1 mechanism of inhibition. Biochemistry 2002; 41: 11997-2009.
145. Verheyden S, Sillen A, Gils A, et al. Tryptophan properties in fluorescence and functional stability of plasminogen activator inhibitor 1. Biophys J 2003; 85: 501-10.
146. Abbott GL, Blouse GE, Perron MJ, et al. 19F NMR studies of plasminogen activator inhibitor-1. Biochemistry 2004; 43: 1507-19.
147. Verhamme I, Kvassman JO, Day DE, et al. Accelerated conversion of human plasminogen activator inhibitor-1 to its latent form by antibody binding. J Biol Chem 1999; 274: 17511-17.
148. Karolin J, Fa M, Wilczynska M, et al. Donor-donor energy migration for determining intramolecular distances in proteins: I. Application of a model to the latent plasminogen activator inhibitor-1 (PAI-1). Biophys J 1998; 74: 11-21.
149. Fa M, Bergstrom F, Hagglof P, et al. The structure of a serpin-protease complex revealed by intramolecular distance measurements using donor-donor energy migration and mapping of interaction sites. Structure 2000; 8: 397-405.
150. Aertgeerts K, De Bondt HL, De Ranter C, et al. Crystallization and X-ray diffraction data of the cleaved form of plasminogen activator inhibitor-1. Proteins 1995; 23: 118-21.
151. Wilczynska M, Fa M, Karolin J, et al. Structural insights into serpin protease complexes reveal the inhibitory mechanism of serpins. Nat Struct Biol 1997; 4: 354-7.
152. Aleshkov SB, Fa M, Karolin J, et al. Biochemical and biophysical studies of reactive center cleaved plasminogen activator inhibitor type 1. The distance between P3 and P1' determined by donor-donor fluorescence energy transfer. J Biol Chem 1996; 271: 21231-8.
153. Strandberg L, Karolin J, Johansson LB, et al. Fluorescence studies on plasminogen activator inhibitor 1: reactive centre cysteine mutants remain active after fluorophore attachment. Thromb Res 1994; 76: 253-67.
154. Backovic M, Stratikos E, Lawrence DA, et al. Structural similarity of the covalent complexes formed between the serpin plasminogen activator inhibitor-1 and the arginine-specific proteinases trypsin, LMW u-PA, HMW u-PA, and t-PA: use of site-specific fluorescent probes of local environment. Protein Sci 2002; 11: 1182-91.
155. Bjorquist P, Ehnebom J, Inghardt T, et al. Epitopes on plasminogen activator inhibitor type 1 important for binding to tissue plasminogen activator. Biochim Biophys Acta 1997; 1341: 87-98.
156. van Zonneveld AJ, van den Berg BM, van Meijer M, et al. Identification of functional interaction sites on proteins using bacteriophage-displayed random epitope libraries. Gene 1995; 167: 49-52.
157. Einholm AP, Pedersen KE, Wind T, et al. Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1. Biochem J 2003; 373: 723-32.
158. Bijnens AP, Gils A, Stassen JM, et al. The distal hinge of the reactive site loop and its proximity: a target to modulate plasminogen activator inhibitor-1 activity. J Biol Chem 2001; 276: 44912-8.
159. Bijnens AP, Gils A, Knockaert I, et al. Importance of the hinge region between α-helix F and the main part of serpins, based upon identification of the epitope of plasminogen activator inhibitor type 1 neutralizing antibodies. J Biol Chem 2000; 275: 6375-80.
160. Bijnens AP, Ngo TH, Gils A, et al. Elucidation of the binding regions of PAI-1 neutralizing antibodies using chimeric variants of human and rat PAI-1. Thromb Haemost 2001; 85: 866-74.
161. Bodker JS, Wind T, Jensen JK, et al. Mapping of the epitope of a monoclonal antibody protecting plasminogen activator inhibitor-1 against inactivating agents. Eur J Biochem 2003; 270: 1672-9.
162. Muehlenweg B, Guthaus E, de Prada NA, et al. Epitope mapping of monoclonal antibodies directed to PAI-1 using PAI-1/PAI-2 chimera and PAI-1-derived synthetic peptides. Thromb Res 2000; 98: 73-81.
163. Stoop AA, Jespers L, Lasters I, et al. High-density mutagenesis by combined DMA shuffling and phage display to assign essential amino acid residues in protein-protein interactions: Application to study structure-function of plasminogen activation inhibitor 1 (PAI-I). J Mol Biol 2000; 301: 1135-47.
164. Wind T, Jensen MA, Andreasen PA. Epitope mapping for four monoclonal antibodies against human plasminogen activator inhibitor type-1 - Implications for antibody-mediated PAI-1-neutralization and vitronectin-binding. Eur J Biochem 2001; 268: 1095-106.
165. Naessens D, Gils A, Compernolle G, et al. Elucidation of the epitope of a latency-inducing antibody: identification of a new molecular target for PAI-1 inhibition. Thromb Haemost 2003; 90: 52-8.
166. Gorlatova NV, Elokdah H, Fan K, et al. Mapping of a conformational epitope on plasminogen activator inhibitor-1 by random mutagenesis. Implications for serpin function. J Biol Chem 2003; 278: 16329-35.
167. Johnson DJ, Huntington JA. Crystal structure of antithrombin in a heparin-bound intermediate state. Biochemistry 2003; 42: 8712-19.
168. Vleugels N, Gils A, Bijnens AP, et al. The importance of helix F in plasminogen activator inhibitor-1. Biochim Biophys Acta 2000; 1476: 20-26.
169. Vleugels N, Gils A, Mannaerts S, et al. Evaluation of the mechanism of inactivation of plasminogen activator inhibitor-1 by monoclonal antibodies using a stable variant. Fibrinolysis 1998; 12: 277-82.
170. York JD, Li P, Gardell SJ. Combinatorial mutagenesis of the reactive site region in plasminogen activator inhibitor I. J Biol Chem 1991; 266: 8495-500.