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)

Various high molecular weight plasmin degradation products of fibrinogen were isolated by chromatographic procedures and investigated to what extent they influence the sedimentation rate of erythrocytes in heparinized serum. Among the early plasminolysis products Fragment X accelerated the sedimentation rate considerably although it was less effective than fibrinogen. Fragment Y showed a weaker but clearly demonstrable agglomerine activity. The late plasminolysis products D and E were ineffective, if applied alone and in concentrations equivalent to the fibrinogen content of plasma. However, they promoted the sedimentation effect of fibrinogen. If present in considerably higher concentrations are Fragments D and E, in absence of fibrinogen, also accelerated the sedimentation rate of erythrocytes significantly. A mixture of D and E was not more effective than the single compounds.
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PMID:[The mechanism of blood cell sedimentation. XVIII. Sedimentation effect of fibrinogen plasminolysis products]. 12 4

A mixture of fragments D, derived from fibrinogen by plasmic degradation, was S-reduced and carboxymethylated. Individual chains were separated by gel filtration on Sephadex G-100 and characterized by peptide mapping, N-terminal amino acid analysis, polyacrylamide electrophoresis in sodium dodecyl sulfate, and amino acid composition. It was demonstrated that all D species contain the same alpha- and beta-chain remnants, having mol. wts of 10 000 and 45 000, respectively. Their heterogeneity was shown to be caused by the gradual degradation of the gamma-chain at its C-terminal end. Denatured fragment D was further degraded with plasmin in the presence of 2 M urea. One beta- (mol. wt 17 000) and two gamma-fragments (mol. wts 5000 and 6000) were split from fragment D, in addition to non-characterized small peptides, leaving behind a plasmin-resistant core, designated as fragment d. Fragment d was in turn reduced and carboxymethylated, and the resulting constituent chains were isolated by chromatography on carboxymethyl-cellulose and Sephadex G-100. The reduced alpha-, beta- and gamma-chain remnants of fragment d were found to have been derived from the N-terminal portion of fragment D and have estimated mol. wts of 9000, 24 000 and 13 000, respectively. A tentative scheme for the conversion of an early fragment D into the core fragment d is proposed. Our results conclusively support the model of asymmetric degradation of fibrinogen, according to which 2 mol of monomeric fragment D are produced from 1 mol of fibrinogen.
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PMID:Plasmic degradation of human fibrinogen. III. Molecular model of the plasmin-resistant disulfide knot in monomeric fragment D. 12 9

Fragment D has been isolated as an apparently single molecular weight species (molecular weight about 100,000) from plasmin digests of humman fibrinogen, using a combination of affinity chromatography on insolubilized "fibrin monomer" and gel filtration. This fragment consists of three chains with molecular weights of 15,000 (Dbeta), 42,500 (Dgamma1) or 39,500 (Dgamma2), and 14,000 (Dalpha) held together by disulfide bonds. The S-carboxymethyl derivatives of the chains have been separated by gel filtration and ion exchange chromatography, and their identity has been confirmed by peptide mapping and immunological analysis. The chain with a molecular weight of 45,000 is a fragment of the Bbeta chain of fibrinogen. The chain derived from the gamma chain of fibrinogen occurred in two molecular forms having molecular weight 42,500 and 39,500. The chain derivative with molecular weight 14,000 is most likely derived from the Aalpha chain of fibrinogen. The chains were characterized by NH2-terminal sequence analysis, amino acid composition, and carbohydrate staining. The two molecular analysis, amino acid composition, and carbohydrate staining. The two molecular forms of the gamma chain appeared to be identical except for an NH2-terminal peptide extension of 23 amino acid residues in the longer chain. The latter has sequences in common with the COOH-terminal part of the gamma chain of the NH2-terminal disulfide knot (BROMBACK, B., BRONDAHL, N. J., HESSEL, B., IWANAGA, S., and WALLEN, P. (1973) J. Biol. Chem. 248, 5806-5820); its NH2-terminal residue being Ala-63 of the gamma chain of fibrinogen.
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PMID:Primary structure of human fibrinogen and fibrin. Isolation and partial characterization of chains of fragment D. 12 79

Fibrinogen, coagulable plasmic derivatives (Fragments X) and Fragments Y, D and E were studied by negative staining electron microscopy. Fragment X obtained from Stage 1 digests and fibrinogen were both globular, while Fragment X of Stage 2 digests appeared as a nodular filament. The Stage 1 and Stage 2 Fragment X preparations had approximately the same molecular weight, but could be differentiated by several subtle differences in polypeptide chain structure. Fragments Y and D were also filamentous, although shorter than Fragment X (Stage 2), and Fragment E appeared as a small, compact or folded filament. These results agree with the concept that fibrinogen consists of a strand of nodules connected by thin strands, folded into a compact, spherical shape. The molecule opens up when stabilizing bonds are disrupted or liberated by plasmin. The data are compatible with a fibrinogen molecule in which the two halves are linked by a single locus of disulfide bonds at the amino terminus and with the asymmetric hypothesis of plasmic degradation to Fragments X, Y, D and E.
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PMID:Electron microscopic studies of plasmic degradation products of fibrinogen. Implications for the disulfide structure of fibrinogen. 12 81

Three Fragment D species (D1, D2, D3) were isolated with time from a plasmin digest of fibrinogen and had molecular weights of 92,999, 86,000 and 82,000 by summation of subunit molecular weights from sodium dodecyl sulfate polyacrylamide gel electrophoresis. Their molecular weights by sedimentation equilibrium ultracentrifugation were 94,000 t87,000, 88,000 to 82, 000, and 76,000 to 70,000 depending on the values calculated for the partial specific volumes. Each of the Fragment D species contained three disulfide-linked subunits derived from the Aalpha, Bbeta, and gamma chains of fibrinogen and differed only in the extent of COOH-terminal degradation of their gamma chain derivatives. Plasmin cleaved Fragment D1 to release the cross-link sites from its gamma' subunit of 38,000 molecular weight; however, the beta'' subunit of 42,000 molecular weight and the alpha'' subunit of 12,000 molecular weight were resistant to further digestion by plasmin. Fragment D isolated from highly cross-linked fibrin had a dimeric structure due to cross-link formation between the gamma' subunits of two fibrinogen Fragment D species. The molecular weight of fibrin Fragment D was 184,000 by summation of subunit molecular weights and 190,000 to 175,000 by sedimentation equilibrium. Cross-linking the gamma chain, as well as incorporating the site-specific fluorescent label monodansyl cadaverine into the gamma chain cross-link acceptor site, prevented its COOH-terminal degradation by plasmin. Therefore, only one species of fibrin Fragment D, as well as only one species of monodansyl cadaverine-labeled fibrin Fragment D monomer, was generated during plasmin digestion. These results show unequivocally that each fibrinogen Fragment D contains only three subunit chains and therefore the digestion of fibrinogen by plasmin must result in the production of two Fragment D molecules from each fibrinogen molecule. The recently proposed model of fibrinogen cleavage that postulates the generation of a single Fragment D with three pairs of subunit chains from each fibrinogen molecule is incorrect. Incorporation of monodansyl cadaverine into the cross-link acceptor sites of the alpha chain did not alter its cleavage by plasmin detectably. A series of monodansyl cadaverine-labeled peptides, which ranged in molecular weight from 40,000 to 23,000, were cleaved from the alpha chain of monodansyl cadaverine-labeled fibrin monomer during the early stages of plasmin digestion. These peptides were degraded progressively to a brightly fluorescent plasmin-resistant peptide of 21,000 molecular weight and a weakly fluorescent peptide of 2,500 molecular weight. Thus both alpha chain cross-link acceptor sites are contained within a peptide segment of 23,000 molecular weight.
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PMID:A re-examination of the cleavage of fibrinogen and fibrin by plasmin. 12 32

The molecular weight of Fragment D derivatives obtained from plasmic digests of fibrinogen and cross-linked fibrin was determined by equilibrium sedimentation and compared with the summated molecular weight of their polypeptide chains observed after electrophoresis of reduced protein in sodium dodecyl sulfate polyacrylamide gels. The measured molecular weight of Fragment D (Stage 2) of fibrinogen is 103 500, which is compatible with a molecule containing only one each of the Aalpha (13 000), Bbeta (43 000) and gamma (39 000) chain remnants. Fragment D-D of cross-linked fibrin has a molecular weight of 189 000, compatible with a molecule containing one isopeptide-bound gamma-gamma chain (80 000) and two each of Bbeta (43 000) and Aalpha (13 000) chain remnants. The NH2-terminal amino acid residues of the Fragment D derivatives were measured quantitatively using a thioacetic-thioglycolic acid method, and molar quantities were calculated on the basis of the molecular weights determined by equilibrium sedimentation. Fragment D preparations obtained from Stage 2 and Stage 3 digests of fibrinogen have 3 mol of NH2-terminal amino acids per molecule, while Fragment D-D has seven. These data support the view that two Fragment D molecules, each of three polypeptide chains, are derived by plasmic degradation from each fibrinogen molecule, and that an isopeptide-bound, six chain Fragment D-D molecule is released from cross-linked fibrin by plasmin. Equlibrium sedimentation measurement of the molecular weights of Fragment X (Stage 1 and Stage 2) and Fragment Y are 265 000 and 148 000, respectively. These values are compatible with asymmetric cleavages of Fragment X to Fragments Y and D (Stage 2), and of Fragment Y to Fragments D (Stage 2) and E, and with a fibrinogen model in which the two halves are joined by disulfide bonds only in the amino-terminal regions.
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PMID:Comparison of the physicochemical properties of fragment D derivatives of fibrinogen and fragment D-D of cross-linked fibrin. 13 Sep 27

The effect of different factor XIII inhibitors (competetive inhibition, interference with active center SH-groups in different ways, Ca2+ depletion) on the sequence of the gamma-dimerization and alpha-polymerization of fibrin is examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAE) (reduced material). They all inhibit either gamma-dimerization and alpha-polymerization or alpha-polymerization alone irrespective of the factor XIII inhibitory mechanism. Non-crosslinked fibrin and fibrin clots of different degrees of crosslinking are digested with plasmin and the lysate tested in SDS-PAE (non-reduced material) and crossed agarose gel immunoelectrophoresis (CAIE). The digests contain Fragment D and Fragment D-D respectively and Fragment E. An additional Fragment E with less anodic mobility in CAIE, and not demonstrable in SDS-PAE, is seen in increasing amounts with increasing gamma-dimerization, alpha-polymerization does not further change the CAIE patterns.
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PMID:gamma-dimerization, alpha-polymerization, and plasmin degradation of human fibrin. Effect of various inhibitors of factor XIII on the patterns in SDS-electrophoresis and crossed immunoelectrophoresis. 13 55

The predominant high molecular weight products of plasmic digestion of human crosslinked fibrin Fragments DD, E and (DD)E complex were purified by column gel filtration in a non-dissociating buffer or by ion-exchange chromatography on DEAE-cellulose. The structure of the degradation products was studied by proteolytic degradation, polyacrylamide gel electrophoresis immunodiffusion and sucrose density gradient centrifugation. Unaltered derivatives were very resistant to proteolytic degradation by plasmin. In the the presence of 10 mM EDTA the (DD)E complex did not dissociate, but similar to Fragment DD, became susceptible to plasmic degradation forming Fragment D derivatives. The (DD)E complex dissociated in 3 M urea at pH 5.5, had an altered conformation as evidenced by its aggregability and by its increased susceptibility to degradation by plasmin resulting in the formation of Fragment d. The gammagamma chain remnants of Fragment DD were attacked first, followed by cleavage of the beta chain remnants. It is concluded that plasmin resistance is a function of the intact structure and it is not directly dependent on the presence of the crosslink bonds or calcium ions.
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PMID:Modification of high molecular weight plasmic degradation products of human crosslinked fibrin. 15 66

Proteolysis of human cross-linked fibrin by plasmin results in the formation of a DD . E complex, and Fragments DD and E as the major degradation products. Three species of Fragment E, which differ both in molecular weights (E1, Mr = 60,000; E2, Mr = 55,000; E3, Mr = 50,000) and in charge, have been isolated from a digest of cross-linked fibrin. Each Fragment E species reacts with monospecific anti-E antiserum. Fragments E1 and E2 bind with Fragment DD to form a DD . E complex but Fragment E3 is inactive. This binding is specific since these Fragments E do not bind to fibrinogen or to degradation products of fibrinogen or of noncross-linked fibrin. Fragments E1 and E2 incubated with plasmin are degraded to Fragment E3, suggesting that the three species represent sequential degradation products. Plasmin-treated Fragments E1 and E2 no longer bind with Fragment DD; therefore, it appears that the peptides cleaved from Fragment E2 by plasmin contain or modify the sites responsible for complex formation. On the other hand, Fragment DD binds not only to Fragments E1 and E2, but also to fibrinogen, Fragments X (Stage 1), X (Stage 2), Y, and NH2-terminal disulfide knot, but only after thrombin treatment, suggesting that Fragment DD binds to complementary sites on the NH2-terminal region of fibrinogen which are exposed after thrombin treatment.
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PMID:Binding phenomena of isolated unique plasmic degradation products of human cross-linked fibrin. 15 98

Fragment E, a terminal plasmin digestion product of fibrinogen or fibrin, contains portions of the alpha, beta, and gamma chains linked by disulfide bonds. In this study, Fragment E from fibrinogen and fully cross-linked fibrin were purified by gel filtration of the soluble fraction from heated plasmin digests of either fibrinogen or fibrin or by step-wise chromatography of terminal plasmin digests of fibrinogen or cross-linked fibrin on DEAE-cellulose. Fibrinogen Fragment E and fibrin Fragment E migrated as single bands with identical mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis or on polyacrylamide gel electrophoresis at pH 3.2 or pH 8.6. After reduction by beta-mercaptoethanol, the two Fragment E species had very similar patterns on sodium dodecyl sulfate gel electrophoresis; each contained three subunits which had molecular weights ranging from 5,000 to 12,000. Only the subunit polypeptide derived from the gamma chain in either Fragment E contained carbohydrate. The two Fragment E species had identical sedimentation coefficients and identical molecular weights by equilibrium ultracentrifugation. The amino acid compositions were indistinguishable. Partial NH2-terminal sequence analyses of fibrinogen Fragment E and fibrin E were identical, indicating that plasmin had cleaved the NH2-terminal regions of the Aalpha or alpha and Bbeta or beta chains of both Fragment E Species.
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PMID:Characterization of fragment E from fibrinogen and cross-linked fibrin. 81 59


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