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)

By virtue of their capacity to bind plasminogen activators and plasminogen, to accelerate plasminogen activation and to protect bound plasmin from inactivation by alpha 2 antiplasmin, cells can harness the broad proteolytic activity of plasmin to their surface. Most cells bind plasminogen with a very high capacity, a relatively low affinity (Kd approximately 1 microM) and recognize the lysine binding sites of the molecule. Gangliosides serve as non-protein plasminogen binding sites, and a subset of membrane proteins with carboxy-terminal lysine residues also serve as receptors. The alpha isoform of enolase possesses a carboxy-terminal lysine and is a prominent plasminogen binding protein of cells. Cells of the monocytoid lineage, including peripheral blood monocytes, can markedly upregulate their expression of plasminogen receptors. The capacity to modulate expression of receptors for fibrinolytic components establishes an additional mechanism by which the cell-surface regulates the function of the plasminogen system.
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PMID:Cellular regulation of fibrinolysis. 165 42

Over the past decade, the existence of cell-surface receptors for components of the plasminogen system, t-PA, u-PA, plasminogen and plasmin, has been demonstrated. Plasminogen receptors have been detected on virtually all cell types tested, and occupancy has also been demonstrated in biological settings. Characteristic features of plasminogen receptors include their relatively low affinity and their extraordinarily high density on many cells. These receptors recognize the lysine binding sites associated with the kringles of plasminogen. Plasminogen receptors include proteins with carboxyl-terminal lysine residues (enolase and annexin II are representatives) and nonproteins, such as gangliosides. Plasminogen binding to cells enhances plasmin activity by augmenting plasminogen activation, increasing the enzymatic activity of plasmin, and protecting plasmin for inactivation by inhibitors. t-PA receptors serve two major functions, clearance and cell-surface localization. The liver is the main organ for t-PA clearance; parenchymal, endothelial and Kupffer cells are all capable of t-PA uptake. Clearance receptors on these cells are heterogeneous and include ones which recognize the carbohydrate side chains of t-PA and ones which take up t-PA: PAI-1 complexes. Receptors which recognize free t-PA also mediate liver clearance, and alpha 2-MR/LRP is a representative of this latter category. Receptors that localize t-PA on cell surfaces serve a profibrinolytic function. Vascular endothelial cells are rich in such receptors, and annexin II is a representative of these t-PA binding sites. Circulating blood cells also bind t-PA, and some of the sites on these cells are shared with plasminogen. Cells of neuronal origin are capable of binding t-PA with high affinity; and amphoterin, a protein involved in neurite outgrowth, may be a neuronal t-PA receptor. Overall, the plasminogen system is one of the most widely distributed and versatile of the cell surface-proteinase systems. By activating bound plasminogen by cell-bound plasminogen activators, the cell harnesses the broad proteolytic activity of plasmin. Cells can then utilize this activity to perform functions such as assisting in cell migration.
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PMID:Receptors for plasminogen and t-PA: an update. 754 65

The plasmin(ogen) binding property of group A streptococci is incriminated in tissue invasion processes. We have characterized a novel 45-kDa protein displaying strong plasmin(ogen) binding activity from the streptococcal surface. Based on its biochemical properties, we confirmed the identity of this protein as alpha-enolase, a key glycolytic enzyme. Dose-dependent alpha-enolase activity, immune electron microscopy of whole streptococci using specific antibodies, and the opsonic nature of polyclonal and monoclonal antibodies concluded the presence of this protein on the streptococcal surface. We, henceforth, termed the 45-kDa protein, SEN (streptococcal surface enolase). SEN is found ubiquitously on the surface of most streptococcal groups and serotypes and showed significantly greater plasmin(ogen) binding affinity compared with previously reported streptococcal plasminogen binding proteins. Both the C-terminal lysine residue of SEN and a region N-terminal to it play a critical role in plasminogen binding. Results from competitive plasminogen binding inhibition assays and cross-linking studies with intact streptococci indicate that SEN contributes significantly to the overall streptococcal ability to bind plasmin(ogen). Our findings, showing both the protected protease activity of SEN-bound plasmin and SEN-specific immune responses, provide evidence for an important role of SEN in the disease process and post-streptococcal autoimmune diseases.
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PMID:alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. 960 64

The glycolytic enzyme enolase is one of the most abundant proteins expressed in fungi and has been shown to be an immunodominant cell-wall-associated antigen of the pathogenic fungus, Candida albicans. Enolase has also been found on the surface of some mammalian cells where it functions as a plasminogen-binding motif and facilitator of plasminogen activation to plasmin. To investigate the immunogenicity of enolase in the opportunistic pathogen, Pneumocystis carinii, the genomic and complementary DNA (cDNA) enolase were cloned and characterized. The predicted protein comprises 433 amino-acid residues and shows extensive homology to other fungal enolases, including those of C. albicans (76%), Aspergillus oryzae (79%) and Saccharomyces cerevisiae (77%). The purified recombinant P. carinii enolase was immunogenic, and may be an important antigen and indicator of P. carinii infection. The active site and conformation metal ion-binding site residues necessary for dimerization and enzyme function are conserved in the predicted P. carinii enolase protein. Enolase of P. carinii is unique among the fungal enolases in that it possesses a catalytic carboxyl-terminal lysyl residue that was necessary and sufficient for the plasminogen-binding activity of the enolase of P. carinii. The activity of the plasminogen binding suggests its involvement in the local regulation of fibrinolysis within the alveolar space.
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PMID:Plasminogen-binding activity of enolase in the opportunistic pathogen Pneumocystis carinii. 1179 55

Many pathogenic bacteria express plasminogen receptors on their surface, which may play a role in the dissemination of organisms by binding plasminogen that, when converted to plasmin, can digest extracellular matrix proteins. A 45-kDa protein was purified from Streptococcus pneumoniae and confirmed as an alpha-enolase by its ability to catalyse the dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate and by N-terminal sequencing. The activity of alpha-enolase was found in the cytoplasm and in whole cells. Activity was also demonstrated in cell wall fractions, which confirmed that alpha-enolase is a cytoplasmic antigen also expressed on the surface of S. pneumoniae. The plasminogen-binding activity of alpha-enolase was examined by Western blot, which showed that purified alpha-enolase was able to bind human plasminogen. Immunoblots of the purified 45-kDa alpha-enolase with 22 sera from patients with pneumococcal disease showed binding in 15 cases, indicating that pneumococcal enolase is immunogenic.
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PMID:Purification of native alpha-enolase from Streptococcus pneumoniae that binds plasminogen and is immunogenic. 1243 62

Enolase represents a multifunctional protein involved in basic energy metabolism and plasminogen binding and activation at the surface of prokaryotic pathogens. A complete cDNA of 1615 bp of an alpha-enolase from Onchocerca volvulus (Ov-ENO) was isolated using a PCR-based approach. The open reading frame encoded for 435 amino acids and the high degree of conservation included the crucial amino acid residues that participate in the formation of the catalytic site, Mg(2+) binding site, and a hydrophobic motif reported to relate to surface expression. A 1089-bp fragment was expressed in a N-terminal 6 x His-tag expression vector in Escherichia coli. By immunohistological analysis using anti-Ov-ENO rabbit antibodies, native enolase could be detected in most tissues of adult O. volvulus, microfilariae, and infective larvae. Intense staining was observed in the muscles, where the energy consumption is high. The purified recombinant protein fragment revealed plasminogen binding activity in a blot-overlay assay employing anti-plasminogen antibodies. In sera from individuals infected with O. volvulus, IgG antibodies reactive with recombinant Ov-ENO were demonstrated by immunoblot and enzyme-linked immunosorbent analyses. The plasminogen-binding property of O. volvulus alpha-enolase may support plasmin-mediated proteolysis including degradation of host's extracellular matrix thereby promoting the migration of larval stages through tissues. The recognition by antibodies in sera of O. volvulus-infected persons indicate an involvement of the protein in the interaction between the parasite and the human host.
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PMID:Molecular cloning of an alpha-enolase from the human filarial parasite Onchocerca volvulus that binds human plasminogen. 1281 29

Infection by the human opportunistic fungal pathogen Candida albicans has been increasing over recent years. In an attempt to understand the molecular mechanism of Candida invasion across host tissues, the relationship of C. albicans enolase to human plasminogen/plasmin was investigated. C. albicans enolase is a cell-surface protein and an immunodominant antigen in infected patients' sera. Plasminogen is an abundant plasma protein. Several lines of evidence support the binding of C. albicans enolase to human plasminogen. Firstly, it was found that various Candida strains were able to bind to plasminogen and its active form, plasmin. Secondly, recombinant Candida enolase was retained in a nickel-chelating affinity column matrix that can bind (125)I-labelled plasminogen or plasmin in a dose-dependent manner. Plasmin(ogen)-specific inhibitors, such as epsilon -aminocaproic acid and aprotinin, can effectively block plasmin-binding activity. Thirdly, as with many plasminogen receptors, binding of Candida enolase to plasmin(ogen) is lysine-dependent, whereas little inhibition occurred with arginine, aspartate and glutamate. Fourthly, immobilized enolase enhanced plasminogen's affinity for streptokinase at least tenfold, as demonstrated by its activation of plasmin activity. To elucidate the biological significance of this result, it was demonstrated that the plasmin(ogen)-bound Candida cells were able to induce fibrinolysis activity in a matrix-gel assay. Furthermore, plasmin-bound Candida cells had an increased ability to cross an in vitro blood-brain barrier system. The results given here indicate that Candida enolase is a plasminogen- and plasmin-binding protein and that the interaction of C. albicans enolase with the plasminogen system may contribute to invasion of the tissue barrier.
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PMID:Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells. 1286 53

Plasmin is a potent extracellular protease specialized in the degradation of fibrin (fibrinolysis). Active plasmin is generated by proteolytic activation of the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Alpha-enolase constitutes a receptor for plasminogen on several leukocyte cell types, serving to localize and promote plasminogen activation pericellularly. However, a role for a -enolase-type plasminogen receptor (PlgR) in myogenesis has never been demonstrated. In this study, we show that C2C12 mouse myoblasts express PlgR, being its expression greatly induced during the differentiation process. A monoclonal antibody against PIgR MAb 11G1, with cell surface-generated plasmin inhibitory abilities, was able to fully abrogate C2C12 myoblast fusion and differentiation in vitro. Moreover, both plasmin activity and PlgR expression were significantly induced in regenerating skeletal muscle in vivo, either in experimentally-injured muscle or in the dystrophic muscle of mdx mouse (an animal model of human Duchenne muscular dystrophy, DMD). The mdx muscle presents better regeneration capacities and less fibrosis than the human DMD muscle; therefore, the increase in PlgR/plasmin activity in mdx muscle suggests an important contribution of the fibrinolytic system in mdx regeneration. This study constitutes the first indication of alpha-enolase-type plasminogen receptor as an important component of skeletal myogenesis, by concentrating and enhancing plasmin generation on the cell surface.
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PMID:Plasmin generation dependent on alpha-enolase-type plasminogen receptor is required for myogenesis. 1451 73

The glycolytic enzyme alpha-enolase represents one of the nonclassical cell surface plasminogen-binding proteins of Streptococcus pneumoniae. In this study we investigated the impact of an internal plasminogen-binding motif of enolase on degradation of extracellular matrix and pneumococcal transmigration. In the presence of host-derived plasminogen activators (PA) tissue-type PA or urokinase PA and plasminogen S. pneumoniae expressing wild-type enolase efficiently degraded Matrigel or extracellular matrix (ECM). In contrast, amino acid substitutions in the nine residue plasminogen-binding motif of enolase significantly reduced degradation of ECM or Matrigel by mutated pneumococci. Similarly, recombinant wild-type enolase but not a mutated enolase derivative that lacks plasminogen-binding activity efficiently degraded ECM and Matrigel, respectively. In particular, bacterial cell enolase-bound plasmin potentiated dissolution of fibrin or laminin and transmigration of pneumococci through a fibrin matrix. In conclusion, these results provide evidence that the enolase is the major plasminogen-binding protein of pneumococci and that the nine residue plasminogen-binding motif of enolase is the key cofactor for plasmin-mediated pneumococcal degradation and transmigration through host ECM.
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PMID:The nine residue plasminogen-binding motif of the pneumococcal enolase is the major cofactor of plasmin-mediated degradation of extracellular matrix, dissolution of fibrin and transmigration. 1611 19

Schistosoma bovis is a ruminant haematic parasite that lives for years in the mesenteric vessels of the host. The aim of this work was to investigate the ability of adult S. bovis worms to interact with plasminogen, a central component in the host fibrinolytic system. Confocal microscopy analysis revealed that plasminogen bound to the tegument surface of the male-but not female-S. bovis worms and that this binding was strongly dependent on lysine residues. It was also observed that a protein extract of the worm tegument (TG) had the capacity to generate plasmin and to enhance the plasmin generation by the tissue-type plasminogen activator. Proteomic analysis of the TG extract identified 10 plasminogen-binding proteins, among which the major ones were enolase, glyceraldehyde-3-phosphate dehydrogenase and actin. This study represents the first report about the binding of plasminogen to Schistosoma sp. proteins.
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PMID:Schistosoma bovis: plasminogen binding in adults and the identification of plasminogen-binding proteins from the worm tegument. 1696 83


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