Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was demonstrated that plasminogen and the plasmin heavy chain form a complex with an immobilized fibrinogen fragment E. The E-fragment interacts, in its turn, with the immobilized heavy chain; this interaction is provided for by the lysin binding sites of the plasminogen molecule. The plasmin light chain having no lysin binding sites is specifically absorbed on the immobilized fragment D, whereas the D-fragment--on the immobilized light chain. The elution is caused by arginine or benzamidine; 6-aminohexanoic acid does not affect this interaction. It is assumed that the interaction of plasminogen and plasmin with fibrin is provided for not only by the lysine binding but also by the benzamidine binding sites of the plasminogen molecule.
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PMID:[Interaction of heavy and light chains of plasmin with fibrinogen E and D fragments]. 624 Sep 93

Glu-plasminogen [native plasminogen (Glu-1-Asn-790)], Lys-plasminogen [plasmin-cleaved fragment of plasminogen (Lys-77-Asn-790)] and miniplasminogen [fragment of plasminogen (Val-440-Asn-790)] were all found to interact specifically with immobilized 6-aminohexyl ligands. The interactions apparently are mediated by a single weak lysine-binding site, termed the AH-site, as seen from the patterns of inhibition obtained from frontal-quantitative-affinity-chromatography experiments with 6-aminohexanoic acid and alpha-N-acetyl-L-lysine methyl ester as competing ligands. The AH-site, in contrast with the strong lysine-binding site of Glu-plasminogen and Lys-plasminogen, may prefer ligands not carrying a free carboxylate function and therefore may interact with lysine side chains of proteins. In Glu-plasminogen the AH-site is present, but is apparently only partially free to react. It is suggested that it participates in an intramolecular complex and that an equilibrium state between two Glu-plasminogen forms exists. It is further suggested that binding of the plasminogens to fibrin is mainly determined by the AH-site.
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PMID:The AH-site of plasminogen and two C-terminal fragments. A weak lysine-binding site preferring ligands not carrying a free carboxylate function. 643 91

The alteration of human and porcine plasmin and the influence of EACA and AMCHA on their activity were investigated. Solutions of both plasmins undergo storage induced alteration, which is best recorded by Chromozym PL, whereas the other chromogenic substrates, S-2251 and S-2302, and casein are less sensitive, and the fibrin plate inadequate. Plasmin amidolytic and fibrinolytic activity is maximally enhanced at 7.6 x 10(-3) M EACA and 6.4 x 10(-4) M AMCHA, and decay through storage is reversed. The caseinolytic activity seems slightly inhibited at the same EACA and AMCHA concentrations. Our results show: 1. The quotient: plasmin activity towards Chromozym PL/Activity towards S-2251 is a useful indicator of "plasmin quality". The quotient decreases markedly upon storage of plasmin solutions. 2. Plasmin stability is improved in the presence of AMCHA. 3. It is valueless to add EACA or AMCHA to inhibit plasmin in amidolytic assays since the chosen concentration enhances the amidolytic activity of already formed plasmin.
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PMID:Different assessment of plasmin with different substrates. In vitro alteration of plasmin, influence of epsilon-aminocaproic acid and tranexamic acid upon its activity. 645 Apr 67

This clinical entity described for the first time by Osler in 1888 presented a great therapeutic problem during many decades because of its severity. Landerman and later on Donaldson and Evans established the pathogenic mechanisms of this disease finding a deficiency in the inhibitor of the first activated component of complement, an alpha 2 aminoglycoprotein, to be the mechanism responsible of the same. More concretely, alterations in the plasmin, kinin and kallikrein systems are those that will lead to a change in vascular permeability with resultant tissue alterations. Four cases of hereditary angioneurotic edema are studied in female patients aged between 15 and 50 years and with family history consistent with angioneurotic familiar edema in which there were six cases of death due to edema of the glottis. Once the diagnosis had been made the patients were subjected to treatment with EACA at doses of 2.5 gm every 6 hours. The determinations of complement were similar in the four cases, with marked decreases in C4 and C1 inhibitor with a decrease in total complement in three cases. Regarding secondary effects, vomiting was found only in one cases, which as the dose was reduced did not necessitate termination of treatment. In summary, considering the results obtained in the cases above, we believe that due to its good tolerance and moderate cost, epsilon-amino-caproic acid at the abovementioned dosage is an excellent pharmacological agent in the treatment of Osler's hereditary angioneurotic edema.
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PMID:Epsilon-amino-caproic acid in the treatment of Osler's hereditary angioneurotic edema. 685 4

A new simple and efficient purification method for alpha 2-antiplasmin is described that is based on the interaction between alpha 2-antiplasmin and a fragment from elastase-digested plasminogen constituting the three N-terminal triple-loop structures in the plasmin A-chain (LBSI). After a single-step adsorption of the alpha 2-antiplasmin from plasminogen-depleted plasma to LBSI-Sepharose and elution with 6-aminohexanoic acid, an 80-90% pure preparation with a yield of 50-60% is obtained. The major impurity is fibrinogen, which can easily be removed by gel filtration, and, as a result, a homogeneous fully active alpha 2-antiplasmin preparation is obtained that has the same properties as previously described for alpha 2-antiplasmin. Evidence is put forward that a form of alpha 2-antiplasmin with less affinity for the lysine-binding sites in plasminogen may exist, even in unfractionated plasma.
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PMID:Affinity-chromatographic purification of human alpha 2-antiplasmin. 690 16

Fibrinolytic activity as well demonstrable in the blood of Rana tigrina. There occurs prompt lysis of diluted plasma; and the plasma euglobulin fraction shows lysis on both unheated and heated fibrin (human or bovine) plates, implying the presence of plasmin-like enzyme in this fraction. The fibrinolytic activity is remarkably inhibited by the erythrocyte-lysate and is moderately enhanced by leucocytes-thrombocytes. EACA suppresses the lysis of dilute cell-free plasma clots at concentrations of 10(-4) M or more, possibly indicating the presence of plasminogen activator in the plasma. Activation of fibrinolysis by human urokinase and not by streptokinase, shows the probable presence of plasminogen and absence of proactivator.
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PMID:Blood fibrinolytic system in rana tigrina. 728 Nov 4

Antisera were raised in rabbits against kringle 4, one of the five homologous domains of human plasminogen, and one which contains a site that binds lysine. A double antibody radioimmunoassay was developed for kringle 4 and used for cross-reactivity studies with plasminogen, kringle 1 + 2 + 3, kringle 5 + light chain, and the plasmin-antiplasmin complex, as competitors of either 125I-kringle 4 or 125I-Lys-plasminogen for binding to anti-kringle 4 antisera. Lys- and Glu-plasminogen caused 50% inhibition of anti-kringle 4 binding to 125I-kringle 4 at ratios of 4 and 20 mol/mol (competitor/kringle 4), respectively. The plasmin-antiplasmin complex behaved similarly to Glu-plasminogen. Kringle 1 + 2 + 3 inhibited at a ratio of about greater than 1000 mol/mol. Our results suggest that most of the surface antigenic sites of kringle 4 are exposed on Lys-plasminogen, Glu-plasminogen, and the plasmin-antiplasmin complex. There may be weak antigenic homology between kringle 4 and kringle 1 + 2 + 3, but there is little or no homology with kringle 5 + light chain and prothrombin fragments 1 and 2. Both 6-aminohexanoic acid and trans-4-(aminomethyl)cyclohexanecarboxylic acid can cause a maximum of 30% inhibition, with the latter being a much better inhibitor. Our results suggest that part of the antibody population is directed against a region of kringle 4 containing a lysine-binding site.
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PMID:Immunochemical characterization of the kringle 4 fragment of human plasminogen. 728 60

Pathological fibrinolysis due to pseudoaneurysms was observed in a patient 4 years after aortobifemoral bypass graft. The patient presented with a pulsatile abdominal mass and ischemic changes in the legs. Excessive bleeding from venipuncture sites prompted coagulation screening, which disclosed rapid clot lysis, fibrin split products, and low fibrinogen suggestive of pathological fibrinolysis. Therapy with epsilon amino caproic acid (EACA, Amicar) controlled the coagulopathy, permitting angiography and operation. Resection of the pseudoaneurysms resulted in resolution of the abnormal fibrinolysis. Normally, there is a balance between coagulation and fibrinolysis protecting against excessive bleeding or clotting. Clot itself is a powerful stimulus for the activation of the fibrinolytic system, although many other factors have been shown to initiate and sustain the process. Fibrinolysis is pathological when the process becomes excessive or inappropriate. Plasminogen is activated to plasmin which digests fibrin. Both plasmin and fibrin split products inhibit polymerization of fibrin monomers (which is the final step in the coagulation cascade in the formation of a stable clot), resulting in an unstable clot which is rapidly lysed. To our knowledge such a coagulopathy has not been reported to be a complication of pseudoaneurysms.
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PMID:Pathological fibrinolysis secondary to pseudoaneurysms. 735 90

Binding of plasmin(ogen) to rat C6 glioma cells is saturable and kringle-domain dependent. This interaction was studied as a model of plasmin(ogen) receptor interactions in nucleated mammalian cells. Apparent 125I-plasmin dissociation from C6 cell binding sites was slow; however, the dissociation rate was increased when the solution contained diisopropyl phosphoryl-plasmin (0.3 microM), fibrinogen (0.16 or 0.8 mg/ml), 1.08 mM D-Val-L-Leu-L-Lys-p-nitroanilide-HCl (S-2251), or epsilon-amino-n-caproic acid (EACA, 5.0 mM). EACA promoted the most rapid dissociation of plasmin. C6 cell-associated plasmin and plasmin in solution demonstrated similar amidase activity. Only specifically bound plasmin (75% of total binding) was active against S-2251. Plasmin that was initially bound to C6 cells digested fibrinogen in a time- and plasmin concentration-dependent manner. alpha 2-Antiplasmin (alpha 2AP, 0.1 microM) completely inhibited fibrinogenolysis by plasmin that was initially C6- or human umbilical vein endothelial-cell associated. Since alpha 2AP reacts selectively with plasmin in solution (minimally with plasmin bound to cells), fibrinogen digestion by cell-associated plasmin probably occurred only after the plasmin dissociated into solution. Crosslinked fibrin clots were formed in uniform layers over C6 cells. If the cells were incubated with plasmin before addition of fibrinogen and thrombin, the clots were rapidly lysed. alpha 2AP incompletely inhibited fibrinolysis when added after fibrin polymerization (44% inhibition with 0.1 microM alpha 2AP). Fibrinolysis was completely inhibited when alpha 2AP was added before fibrin polymerization. These studies suggest that plasmin must first dissociate from cellular binding sites to mediate fibrinogenolysis or fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinogenolytic and fibrinolytic activity of cell-associated plasmin. 767 97

The effects of alpha 2-antiplasmin and fibrin on the activation of plasminogen by recombinant staphylokinase (STAR) were studied in an effort to elucidate further the molecular basis of the fibrin-specificity of this fibrinolytic agent. In purified systems consisting of 1.5 mumol/L intact or low-M(r) plasminogen and 3 mumol/L alpha 2-antiplasmin, at 37 degrees C and in the absence of fibrin, STAR did not induce plasminogen activation and plasmin-alpha 2-antiplasmin complex (PAP) formation. Addition of a purified fibrin clot (30% vol at a concentration of 3 mg/mL) to mixtures containing intact plasminogen caused approximately 40% plasminogen activation within 2 hours, whereas in mixtures containing low-M(r) plasminogen, no activation was observed. In contrast, 10 nmol/L streptokinase (SK) induced 74% to 100% plasminogen activation within 2 hours in mixtures containing either intact or low-M(r) plasminogen, in both the absence and the presence of fibrin. In citrated human plasma in the absence of fibrin, 30 nmol/L STAR did not induce measurable plasminogen activation and PAP formation (< 1.5% within 2 hours), whereas addition of a plasma clot (12% vol) resulted in complete clot lysis and conversion of 19% +/- 8% of the plasminogen to PAP within 2 hours. Addition of a second plasma clot produced 23% +/- 2% additional plasminogen activation. Equipotent concentrations for plasma clot lysis of SK (100 nmol/L) induced 54% +/- 11% plasminogen activation in the absence and 49% +/- 16% in the presence of fibrin. Addition of 50 mmol/L 6-aminohexanoic acid (6-AHA) abolished the effect of fibrin on plasminogen activation with STAR, but not on activation with SK. In alpha 2-antiplasmin-depleted human plasma in the absence of fibrin, 30 nmol/L STAR did not induce fibrinogen breakdown (> 90% residual fibrinogen after 6 hours), whereas 30 nmol/L preformed plasmin-STAR complex induced extensive fibrinogen degradation (70% within 20 minutes). Thus, in the absence of fibrin, alpha 2-antiplasmin inhibits the activation of plasminogen by STAR, by preventing generation of active plasmin-STAR complex. Fibrin stimulates plasminogen activation by STAR via mechanisms involving the lysine-binding sites of plasminogen, probably by facilitating the generation of plasmin-STAR complex and by delaying its inhibition at the clot surface.
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PMID:Regulation by alpha 2-antiplasmin and fibrin of the activation of plasminogen with recombinant staphylokinase in plasma. 768 90


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