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Isolation, characterization, and cDNA cloning of a vampire bat salivary plasminogen activator
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The recombinant Escherichia coli-derived protease domain of tissue-type plasminogen activator is a potent and fibrin specific fibrinolytic agent
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Probing structure/function relationships of tissue-type plasminogen activator by site-specific mutagenesis
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of outstanding interest. Presents a concise summary of gene-targeting studies in fibrinolysis and coagulation and discusses the derived role of the molecules involved.
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Carmeliet P, Collen D. Genetic analysis of the plasminogen and coagulation system in mice. of outstanding interest Haemostasis. 26(suppl 4):1996;132-153 Presents a concise summary of gene-targeting studies in fibrinolysis and coagulation and discusses the derived role of the molecules involved.
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Carmeliet, P.1
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Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4 Å resolution
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Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic aicd and antifibrinolytic drug
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The solution structure and backbone dynamics of the fibronectin type 1 and epidermal growth factor-like pair of modules of tissue-type plasminogen activator
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Smith BO, Downing AK, Driscoll PC, Dudgeon TJ, Campbell ID. The solution structure and backbone dynamics of the fibronectin type 1 and epidermal growth factor-like pair of modules of tissue-type plasminogen activator. Structure. 3:1995;823-833.
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The 2.3 Å crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator
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of outstanding interest. The exact structure of the proteolytic domain of human t-PA allows conclusions on specificity, plasminogen cleavage site geometry, ETI binding, single-chain stabilisation and kringle 2 domain attachment.
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Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W. The 2.3 Å crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator. of outstanding interest J Mol Biol. 258:1996;117-135 The exact structure of the proteolytic domain of human t-PA allows conclusions on specificity, plasminogen cleavage site geometry, ETI binding, single-chain stabilisation and kringle 2 domain attachment.
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19
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0030875839
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Structural mapping of the active site specificity determinants of human tissue-type plasminogen activator
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of outstanding interest. The crystal structure of the 1-PA proteolytic domain in complex with a synthetic bis-benzamidine inhibitor is presented and shows that the S3/S4 groove of t-PA prefers arginine and phenylalanine sidechains, in agreement with t-PA's preference for D-Phe/Arg residues at P3.
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Renatus M, Bode W, Huber R, Stürzebecher J, Prasa D, Fischer S, Kohnert U, Stubbs MT. Structural mapping of the active site specificity determinants of human tissue-type plasminogen activator. of outstanding interest J Biol Chem. 272:1997;21713-21719 The crystal structure of the 1-PA proteolytic domain in complex with a synthetic bis-benzamidine inhibitor is presented and shows that the S3/S4 groove of t-PA prefers arginine and phenylalanine sidechains, in agreement with t-PA's preference for D-Phe/Arg residues at P3.
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J Biol Chem
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Renatus, M.1
Bode, W.2
Huber, R.3
Stürzebecher, J.4
Prasa, D.5
Fischer, S.6
Kohnert, U.7
Stubbs, M.T.8
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20
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0030742394
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Lysine 156 promotes the anomalous proenzyme activity of t-PA: X-ray crystal structure of single-chain human t-PA
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of outstanding interest. Lys 156, in single-chain t-PA, is shown to form a buried salt bridge with Asp 194, whose "internal" placement is correlated with a functional binding site. A set of secondary interactions required for Lys 156 to fulfil its 'activating' role are indentified.
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Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W. Lysine 156 promotes the anomalous proenzyme activity of t-PA: X-ray crystal structure of single-chain human t-PA. of outstanding interest EMBO J. 16:1997;4797-4805 Lys 156, in single-chain t-PA, is shown to form a buried salt bridge with Asp 194, whose "internal" placement is correlated with a functional binding site. A set of secondary interactions required for Lys 156 to fulfil its 'activating' role are indentified.
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EMBO J
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Renatus, M.1
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Bode, W.7
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21
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Catalytic domain structure of vampire bat plasminogen activator: A molecular paradigm for proteolysis without activation cleavage
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of outstanding interest. In v-PA. Lys 156 shielded from bulk solvent by the noncleavable 'activation loop' is involved in salt-bridge formation with asp 194, whose 'internal' conformation is associated with a functional binding site. This 'activation' has the same molecular basis as the activity of the single-chain form of human t-PA
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Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning W-D, Bode W. Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage. of outstanding interest Biochemistry. 1997; In v-PA. Lys 156 shielded from bulk solvent by the noncleavable 'activation loop' is involved in salt-bridge formation with asp 194, whose 'internal' conformation is associated with a functional binding site. This 'activation' has the same molecular basis as the activity of the single-chain form of human t-PA.
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Biochemistry
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Renatus, M.1
Stubbs, M.T.2
Huber, R.3
Bringmann, P.4
Donner, P.5
Schleuning, W.-D.6
Bode, W.7
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Tachias, K.1
Madison, E.L.2
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23
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0029800327
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Converting tissue-type plasminogen activator into a zymogen
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of outstanding interest. This paper shows conclusively by mutating His144 to aspartate and glutamate that in the absence of fibrin His144 is of high importance for the catalytic activity of the single-chain form of t-PA
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Tachias K, Madison EL. Converting tissue-type plasminogen activator into a zymogen. of outstanding interest J Biol Chem. 271:1996;28749-28752 This paper shows conclusively by mutating His144 to aspartate and glutamate that in the absence of fibrin His144 is of high importance for the catalytic activity of the single-chain form of t-PA.
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J Biol Chem
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Tachias, K.1
Madison, E.L.2
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24
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0031036522
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Converting tissue-type plasminogen activator into a zymogen
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of outstanding interest. This paper shows by mutating Lys156 to tyrosine that Lys156 essentially contributes to the activity of single-chain t-PA and suggests mutations that might extend the therapeutic range.
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Tachias K, Madison EL. Converting tissue-type plasminogen activator into a zymogen. of outstanding interest J Biol Chem. 272:1997;28-31 This paper shows by mutating Lys156 to tyrosine that Lys156 essentially contributes to the activity of single-chain t-PA and suggests mutations that might extend the therapeutic range.
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J Biol Chem
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Tachias, K.1
Madison, E.L.2
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Site-directed mutagenesis in human tissue-type plasminogen activator
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0026774622
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Tyrosine 67 in the epidermal growth factor-like domain of tissue-type plasminogen activator is important for clearance by a specific hepatic receptor
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Bassel-Duby R, Jiang NY, Bittick T, Madison E, McGookey D, Orth K, Shohet R, Sambrook J, Gething MJ. Tyrosine 67 in the epidermal growth factor-like domain of tissue-type plasminogen activator is important for clearance by a specific hepatic receptor. J Biol Chem. 267:1992;9668-9677.
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Complexation of the tissue plasminogen activator protease with benzamidine-type inhibitors: Interference by the kringle 2 module
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Eastman, D.1
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A slow clearing. fibrin-specific, PAI-1 resistant variant of t-PA (T103N, KHRR 296-299 AAAA).
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Paoni NF, Keyt BA, Refino CJ, Chow AM, Nguyen HV, Bereleau LT, Badillo J, Pea LC, Brady K, Wurm FM, et al. A slow clearing. fibrin-specific, PAI-1 resistant variant of t-PA (T103N, KHRR 296-299 AAAA). Thromb Haemostasis. 70:1993;307-312.
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Chow, A.M.4
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Badillo, J.7
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Brady, K.9
Wurm, F.M.10
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35
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0027081333
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Mapping of the catalytic site of CHO-t-PA and the t-PA variant BM 06.022 by synthetic inhibitors and substrates
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Stürzebecher J, Neumann U, Kohnert U, Kresse G-B, Fischer S. Mapping of the catalytic site of CHO-t-PA and the t-PA variant BM 06.022 by synthetic inhibitors and substrates. Protein Sci. 1:1992;1007-1013.
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Stürzebecher, J.1
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Fischer, S.5
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36
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0029645121
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The crystal structure of the catalytic domain of human urokinase-type plasminogen activator
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Spraggon G, Phillips C, Nowak UK, Ponting CP, Saunders D, Dobson CM, Stuart DI, Jones EY. The crystal structure of the catalytic domain of human urokinase-type plasminogen activator. Structure. 3:1995;681-691.
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Spraggon, G.1
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37
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Distinguishing the specificities of closely related proteases. Role of P3 in substrate and inhibitor discrimination between tissue-type plasminogen activator and urokinase
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of outstanding interest. This paper identifies, using a novel substrate subtraction, display library peptides (with arginine and serine-P3, respectively) that are particularly selective for either t-PA or u-PA and shows that corresponding substitutions in P3 and P4 render PAI-1 more t-PA specific.
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Ke S-H, Coombs GS, Tachias K, Navre M, Corey DR, Madison EL. Distinguishing the specificities of closely related proteases. Role of P3 in substrate and inhibitor discrimination between tissue-type plasminogen activator and urokinase. of outstanding interest J Biol Chem. 272:1997;16603-16609 This paper identifies, using a novel substrate subtraction, display library peptides (with arginine and serine-P3, respectively) that are particularly selective for either t-PA or u-PA and shows that corresponding substitutions in P3 and P4 render PAI-1 more t-PA specific.
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J Biol Chem
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Ke, S.-H.1
Coombs, G.S.2
Tachias, K.3
Navre, M.4
Corey, D.R.5
Madison, E.L.6
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0028923753
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Substrate specificity of tissue type plasminogen activator. Characterization of the fibrin independent specificity of t-PA for plasminogen
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Madison EL, Coombs GS, Corey DR. Substrate specificity of tissue type plasminogen activator. Characterization of the fibrin independent specificity of t-PA for plasminogen. J Biol Chem. 270:1995;7558-7562.
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Madison, E.L.1
Coombs, G.S.2
Corey, D.R.3
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0030064016
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Distinct mechanisms contribute to stingent substrate specificity of tissue-type plasminogen activator
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Coombs GS, Dang AT, Madison EL, Corey DR. Distinct mechanisms contribute to stingent substrate specificity of tissue-type plasminogen activator. J Biol Chem. 271:1996;4461-4467.
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Coombs, G.S.1
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Madison, E.L.3
Corey, D.R.4
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40
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0031026330
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Identification of a hydrophobic exosite on tissue type plasminogen activator that modulates specificity for plasminogen
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of outstanding interest. A hydrophobic edge located below the active-site cleft of t-PA makes an important secondary site for interaction with plasminogen
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Ke S-H, Taschias K, Lamba D, Bode W, Madison EL. Identification of a hydrophobic exosite on tissue type plasminogen activator that modulates specificity for plasminogen. of outstanding interest J Biol Chem. 272:1997;1811-1816 A hydrophobic edge located below the active-site cleft of t-PA makes an important secondary site for interaction with plasminogen.
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J Biol Chem
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Ke, S.-H.1
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