Subscribe to RSS
Effect of staphylokinase-derived nonadecapeptide on the activation of plasminogen
25 August 2006
Accepted after resubmission 02 March 2007
24 November 2017 (online)
Staphylokinase (SAK) expresses plasminogen activator (PA) activity by forming a complex with plasmin. The interaction between the plasmin-SAK complex and plasminogen was investigated using synthesized peptides, which were constructed according to the amino acid sequence of the SAK molecule.A synthetic nonadecapeptide (SAK22–40) corresponding to Glu22-Leu40 by the SAK molecule enhanced the activation of Glu-plasminogen by the plasmin-SAK complex.Analysis of IAsys resonant mirror biosensor showed that SAK22–40 bound to Glu-plasminogen.This binding was completely inhibited by IgG against the B-chain in the plasminogen molecule. But, this binding was not inhibited by IgG against lysine-binding sites (LBS) of the A-chain in the plasminogen molecule. The substitution of Lys35 with Ala in SAK22–40 did not enhance the activation of Glu-plasminogen by the plasmin-SAK complex. When SAK22–40 was administrated in a mouse thrombosis model, earlier recanalization was observed than in mice with vehicle administration. Thus, a newly synthesized peptide, SAK22–40 enhanced Glu-plasminogen activation and induced effective thrombolysis.
- 1 Lack CH. Staphylokinase: an activator of plasma protease. Nature 1948; 161: 559-560.
- 2 Lijnen HR, Van Hoef B, De Cock F. et al. On the mechanism of fibrin-specific plasminogen activation by staphylokinase. J Biol Chem 1991; 266: 11826-11832.
- 3 Sakai M, Watanuki M, Matsuo O. Mechanism of fibrin- specific fibrinolysis by staphylokinase: participation of α2-plasmin inhibitor. Biochem Biophys Res Commun 1989; 162: 830-837.
- 4 Okada K, Ueshima S, Takaishi T. et al. Effects of fibrin and α2-antiplasmin on plasminogen activation by staphylokinase. Am J Hemat 1996; 53: 151-157.
- 5 Matsuo O, Okada K, Fukao H. et al. Thrombolytic properties of staphylokinase. Blood 1990; 76: 925-929.
- 6 Haijar KA. Cellular receptors in the regulation of plasmin generation. Thromb Haemost 1995; 74: 294-301.
- 7 Molgaard L, Ponting CP, Christensen U. Glycosylation at Asn-289 facilitates the ligand-induced conformational changes of human Glu-plasminogen. FEBS Lett 1997; 405: 363-368.
- 8 Petersen LC, Handest P, Brender J. et al. A sensitive solid-phase immunosorbent assay for tissue-type plasminogen activator activity in plasma using trinitrobenzoylated poly-D-lysine as a stimulator for plasminogen activation. Thromb Haemost 1987; 57: 205-211.
- 9 Ohyama S, Harada T, Chikanishi T. et al. Nonlysine- analog plasmin(ogen) modulators promote autoproteolytic generation of plasminogen fragments with angiostatin-like activity. Eur J Biochem 2004; 271: 809-820.
- 10 Rabijns A, De Bondt HL, De Ranter C. Three-dimensional structure of staphylokinase, a plasminogen activator with therapeutic potential. Nature Struct Biol 1997; 04: 357-360.
- 11 Parry MAA, Fernandez-Catalan C, Bergner A. et al. The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor- substrate complex in action. Nature Struct Biol 1998; 05: 917-923.
- 12 Jespers L, Van Herzeele N, Lijnen HR. et al. Arginine719 in human plasminogen mediator formation of the staphylokinase:plasmin activator complex. Biochemistry 1998; 37: 6380-6386.
- 13 Jespers L, Vanwetswinkel S, Lijnen HR. et al. Structural and functional basis of plasminogen activation by staphylokinase. Thromb Haemost 1999; 81: 479-485.
- 14 Sako T. Overproduction of staphylokinase in Escherichia coli and its characterization. Eur J Biochem 1985; 149: 557-563.
- 15 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096.
- 16 Okada K, Nonaka T, Matsumoto H. et al. Effects of α2-plasmin inhibitor on plasminogen activation by staphylokinase/ plasminogen complex. Thromb Res 1994; 76: 211-220.
- 17 Nieuwenhuizen W, Verheigen JH, Vermond A. et al. Plasminogen activation by tissue activator is accelerated in the presence of fibrin(ogen) cyanogens bromide fragment FCB-2. Biochem Biophys Acta 1983; 755: 531-533.
- 18 Okada K, Ueshima S, Fukao H. et al. Analysis of complex formation between plasmin(ogen) and staphylokinase or streptokinase. Arch Biochem Biophys 2001; 393: 330-341.
- 19 Okada K, Ueshima S, Tanaka M. et al. Analysis of plasminogen activation by the plasmin-staphylokinase complex in plasma of α2-antiplasmin-deficient mice. Blood Coagul Fibrin 2000; 11: 645-655.
- 20 Ueshima S, Matsuno H, Hayashi M. et al. Function of tissue-type plasminogen activator releaser on vascular endothelial cells and thrombolysis in vivo. Thromb Haemost 2002; 87: 1069-1074.
- 21 Mangel WF, Lin BH, Ramakrishnan V. Characterization of an extremely large, ligand-induced conformational change in plasminogen. Science 1990; 248: 69-73.
- 22 An SS, Carreno C, Marti DN, Schaller J. et al. Lysine- 50 is a likely site for anchoring the plasminogen N-terminal peptide to lysine-binding kringles. Protein Sci 1998; 07: 1960-1969.
- 23 Sun Z, Chen Y, Wang P. et al. The blockage of the high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochim Biophy Acta 2002; 1596: 182-192.
- 24 Yonekawa O, Vermond A, Nieuwenhuizen W. Localization in the fibrinogen gamma-chain of a new site that is involved in the acceleration of the tissue-type plasminogen activator-catalysed activation of plasminogen. Biochem J 1992; 283: 187-191.