Human plasminogen

Although the precise mechanism of plasminogen activation is unknown, three principal theories have developed based on studies of the in vitro activation of native human plasminogen. Activation of native Glu-plasminogen in the absence of any plasmin inhibitor yields Lys —plasmin plus the so-called pre-activation peptides (PAP) formed by cleavage at LySg2 S E3 Activation takes place by a two-step mechanism in... 

E2. Edelberg, J. M., Gonzalez-Gronow, M., and Pizzo, S. V., Lipoprotein(a) inhibits streptokinase-mediated activation of human plasminogen. Biochemistry 28, 2370-2374 (1989). 

Anistreplase is a complex of human plasminogen and streptokinase in which an anisoyl group has been introduced in the plasminogen... 

Anistreplase (anisoylated plasminogen streptokinase activator complex APSAC) consists of a complex of purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme s active site. When administered, the acyl group spontaneously hydrolyzes, freeing the activated streptokinase-proactivator complex. This product (recently discontinued in the USA) allows for rapid intravenous injection, greater clot selectivity (ie, more activity on plasminogen associated with clots than on free plasminogen in the blood), and more thrombolytic activity. 

The molecular weights and sedimentation coefficients of human plasminogen and plas-min (p = 1.40 g cm-3) are as follows ... 

Structural Formula Binary complex of streptokinase and human plasminogen... 

Davidson DJ, Fraser MJ, Castellino FJ (1990) Oligosaccharide processing in the expression of human plasminogen cDNA by lepidopteran insect (Spodoptera frugiperda) cells. Biochemistry. 29(23) 5584-90. 

Pannekoek H, van Meijer M, Schleef RR, Loskutoff DJ, Barbas CD, Functional display of human plasminogen-activator inhibitor I (PAI-1) on phages Novel perspectives for structure-function analysis by error-prone DNA synthesis, Gene, 128 135-140, 1993. 

Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol 1985 100(l) 86-92. 

In addition to the described preparation, for continuous infusion of a thrombolytic test solution a polyethylene catheter is inserted in the jugular vein. One and a half hours after implantation of the wire coil, the test compound or the vehicle (controls) is infused for up to 2.5 h. The wire coil is then removed and the protein content of thrombi is determined (see above). Bernat et al. (1986) demonstrated the fibrinolytic activity of urokinase and streptokinase-human plasminogen complex in this model. 

Bernat A, Vallee E, Maffrand JP (1986) A simple experimental model of thrombolysis in the rat effect of urokinase and of the complex human plasminogen-streptokinase. Thromb Res 44 Suppl VI 112... 

Shulman, S., Alkjaersig, N., and Sherry, S., Physicochemical studies on human plasminogen (profibrinolysin) and plasmin (fibrinolysin). J. Biol. Chem. 233, 91-97... 

W2. Wiman, B., and Wallen, P. M., Amino-acid sequence of the cyanogen-bromide fragment from human plasminogen that forms the linkage between the plasmin chains. Eur. J. Biochem. 58, 539-547 (1975). 

Catheter-based, adenoviral Human plasminogen Rat carotid artery Murakami et al. DeYoung et al. 

Cockell, C.S., et ah. Evidence that the conformation of unliganded human plasminogen is maintained via an intramolecular interaction between the lysine-binding site of kringle 5 and the N-terminal peptide. Biochem J 1998, 333, 99-105. 

Terzyan, S., et ah. Characterization of Lys-698 to met substitution in human plasminogen catalytic domain. Proteins 2004, 56, 277-284. 

R. A. Atkinson and R, J. P, Williams, J. Mol. Biol., 212(3), 541 (1990). Solution Structure of the Kringle 4 Domain from Human Plasminogen by H Nuclear Magnetic Resonance Spectroscopy and Distance Geometry. 

The immobilized F-II cleaves human plasminogen at four hydrolytic sites Lys77-Arg7g, Arg342-Met343, Alam-Ala s and Arg557-Ile558... 

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