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

---

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

Macrophage adhesion molecule (MAM) is a surface heterodimer consisting of the trypsin- and plasmin-sensitive glycopeptide gp160 (MAM-alpha) and the glycopeptide gp93 (MAM-beta). MAM, which is the guinea pig analogue of Mo1 and Mac-1, was purified from detergent lysates of peritoneal neutrophils by lentil lectin chromatography and M2-antibody chromatography. The pure heterodimer molecule was dissociated by acidic conditions (pH 3.5), and MAM-alpha and MAM-beta were separated by M7-antibody chromatography. MAM-beta is an approximately 640 amino acid residue polypeptide with exceptionally high cysteine content. At 7.2 residues per 100 amino acids, Cys/2 of MAM-beta is more than 3 times the mean for 200 purified proteins. Reactivity with six beta-subunit-specific monoclonal antibodies recognizing at least four epitopes demonstrated that intrapeptide disulfide bonds are required to maintain the structure of MAM-beta. All six antibodies failed to react when MAM-beta was treated with reducing agents. MAM-beta is 18% carbohydrate; the major monosaccharides are mannose, N-acetylglucosamine, galactose, and sialic acid. MAM-beta is estimated to contain five to six N-linked carbohydrate units. MAM-alpha is an approximately 1100-residue polypeptide with lower Cys/2 content (2.0 residues per 100 amino acid residues). MAM-alpha is 21% carbohydrate. The major monosaccharides are mannose, N-acetylglucosamine, galactose, and sialic acid; the mannose content is higher in MAM-alpha than MAM-beta. MAM-alpha is estimated to contain 12 N-linked carbohydrate units.
...
PMID:Purification, composition, and structure of macrophage adhesion molecule. 334 44

The ability of B16-F10 mouse melanoma cells to cross an amnion basement membrane was determined in the presence of strong inhibitors of both serine and cysteine proteases. The concentrations of inhibitors were at orders of magnitude higher than their Ki values to serine and cysteine proteases implicated in metastasis, thus ensuring a complete inhibition for tumor secreted proteases such as cathepsin B-like proteases, plasminogen activators, and plasmin. Under these conditions of high serine and cysteine protease inhibitor concentrations, no significant decrease in B16-F10 melanoma cell invasion through the amnion was observed. Separate experiments showed that the inhibitors were neither toxic to the cells nor degraded. The results show that neither tumor cell secreted cathepsin B-like proteases nor plasminogen activator have a controlling role in basement membrane crossing in this metastatic model. A possible role for tumor cell membrane proteases in basement membrane invasion, in which the substrates of the protease bind to receptor sites near a membrane associated proteolytic activity, is not eliminated.
...
PMID:Inhibition of proteolytic enzymes in the in vitro amnion model for basement membrane invasion. 352 1

The specificity and reactivity of human alpha 1-proteinase inhibitor has been investigated by in vitro mutagenesis of the reactive site P1 methionine 358 residue to alanine 358 and cysteine 358. A comparison of the second-order association rates of both uncharged mutants with 9 serine proteinases indicated that each reacted similarly to either the normal plasma inhibitor or to a mutant containing valine in this position (Travis, J., Owen, M., George, P., Carrell, R., Rosenberg, S., Hallewell, R. A., and Barr, P. J. (1985) J. Biol. Chem. 260, 4384-4389) when tested against either neutrophil or pancreatic elastase. However, oxidation, carboxymethylation, or aminoethylation of the cysteine mutant to yield a charged P1 residue resulted in a significant decrease in association rates with both elastolytic enzymes, and aminoethylation created an excellent trypsin and plasmin inhibitor. These results indicate that the specificity of alpha 1-proteinase inhibitor is determined in a general manner by the class of amino acid residue in the P1 position. Substitution within the same category, such as from valine to alanine or cysteine among the aliphatic hydrophobic residues, has little effect on association rates with the elastolytic enzymes tested. However, alteration from an uncharged to a charged residue may cause considerable changes in both inhibitor specificity and reactivity as noted here with the cysteine derivatives and also previously with a natural variant in which methionine 358 to arginine 358 conversion resulted in the production of a potent thrombin inhibitor (Owen, M. C., Brennan, S. O., Lewis, J. H., and Carrell, R. W. (1983) N. Engl. J. Med. 309, 694-698).
...
PMID:Recombinant DNA-derived forms of human alpha 1-proteinase inhibitor. Studies on the alanine 358 and cysteine 358 substituted mutants. 352 44

1. The proteolytic activities of several gamma-globulin preparations were tested. These included sulphate-precipitated human and bovine preparations and human and bovine Cohn fraction II preparations as well as purified gamma-globulin preparations. Up to 14mg. of diffusible peptides and glycopeptides/g. of gamma-globulin was liberated after dialysis and up to 10mg. of peptides/g. after incubation and trichloroacetic acid precipitation, as products of the degradation process in incubated gamma-globulin. 2. in-Aminohexanoic acid and p-chloromercuribenzoic acid, as well as heating at 60 degrees for 40min., were shown to inhibit strongly these proteolytic activities. Streptokinase was shown to activate strongly the proteolytic activity of all the human preparations (sulphate-precipitated, Cohn fraction II, and purified gamma-globulin). 3. Two distinct pH optima were shown for human and bovine gamma-globulin preparations: one at pH8, the other at pH3.8 (the latter activity could be demonstrated only in the presence of cysteine). 4. Both (131)I-labelled human Cohn fraction II and bovine fibrinogen were attacked by a sulphate-precipitated preparation of gamma-globulin. Of the synthetic substrates tested toluene-p-sulphonyl-l-arginine methyl ester was hydrolysed by both the sulphate-precipitated and Cohn fraction II preparations, as was benzoyl-l-arginine amide at pH5, but only in the presence of cysteine. 5. These data are interpreted to indicate that at least two enzymes are present in gamma-globulin preparations, one being similar to the plasmin system, the other similar to cathepsin B.
...
PMID:Studies on the proteolytic activity of gamma-globulin preparations. 416 42

SOLUBILIZED PROTEIN DERIVED FROM HUMAN PLATELETS WAS FRACTIONATED BY DEAE CELLULOSE COLUMN CHROMATOGRAPHY AND ANALYZED FOR PROTEASE ACTIVITY USING THREE SUBSTRATES: denatured bovine hemoglobin, alpha casein, and purified plasminogen-free human fibrinogen. A protein fraction was found with proteolytic activity which was heat labile and not attributable to plasmin. The activity was not potentiated by cysteine or inhibited by iodoacetamide. Studies of pH optima indicated a broad range of enzyme activity with peaks in both the acid and alkaline region. Cathepsin A activity was detected in the platelet protease fraction by hydrolysis of the synthetic substrate N-carbobenzoxy-alpha-L-glutamyl-L-tyrosine. Similar proteolytic activity was found when the proteins derived from isolated platelet granules were examined. The results indicate that human platelets possess potent intracellular proteolytic enzymes. The relationship of this proteolytic activity to the hemostatic process is discussed.
...
PMID:Studies on human platelet protease activity. 423 82

The porcine uterus secretes a group of basic, low molecular weight protease inhibitors under the influence of progesterone, but not estrogen. One of these inhibitors (Mr approximately 14,500) which inhibits trypsin, plasmin, and chymotrypsin, but not other proteases tested, has been purified 10- to 15-fold from uterine secretions of pseudopregnant pigs using Sephadex G-100 chromatography, CM-cellulose ion exchange chromatography, and Sephadex G-50 or Bio-Gel P-10 chromatography. The inhibitor which is relatively heat- and pH-stable forms a 1:1 molar complex with trypsin which is not dissociated in sodium dodecyl sulfate except by boiling. Chymotrypsin appears to bind at the same site on the inhibitor as trypsin. The inhibitor is high in half-cysteine residues and basic amino acids, and appears not to be a glycoprotein. Antiserum has been raised against the purified inhibitor in rabbits and used to test its distribution in pigs using the immunoperoxidase-staining technique on tissue sections. The inhibitor is associated only with the glandular and surface epithelium of the uterus. Endometrial explants from pseudopregnant animals, cultured in presence of L-[3H]leucine, release the inhibitor in radioactive form indicating that it is a uterine product. The antiserum against the inhibitor cross-reacts with at least three other, basic, low molecular weights plasmin/trypsin inhibitors in porcine uterine secretions, suggesting that a family of isoinhibitors exists which may constitute up to 15% of the protein in porcine uterine secretions. The inhibitor(s) appears to coat and to be taken up by the trophoectoderm cells of the elongating blastocyst during pregnancy. It is suggested that the inhibitors may serve to protect the uterus from proteases released by the porcine trophoblast or to prevent degradation of essential macromolecules, such as uteroferrin, which have to be taken up by the conceptus.
...
PMID:Purification and properties of a progesterone-induced plasmin/trypsin inhibitor from uterine secretions of pigs and its immunocytochemical localization in the pregnant uterus. 621 38

Proteinases are classified into four groups according to their catalytic mechanisms: the serine, cysteine (thiol), aspartic (carboxyl), and metallo-proteinases. Neutrophil granulocytes contain a variety of neutral proteinases and two acid proteinases. Lysosomal proteinases are released from cells during phagocytosis, cell death, or exposure to antigen-antibody complexes, complement factors, and toxins. Under pathological conditions, massive proteinase release may cause tissue injury and degradation of plasma proteins. Plasma proteolytic activity is controlled by inhibitors of blood systems (antithrombin III, C1 inhibitor, and plasmin inhibitor) and by inhibitors against proteinases of various body cells (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, beta 1-collagenase inhibitor, and inter-alpha-trypsin inhibitor). Intracellular proteinases are controlled by different cytosolic inhibitors. In hypercatabolic states (septicemia, trauma, burns), the concentrations of many plasma proteins, including proteinase inhibitors, are decreased. Kallikrein-kinin, complement, and fibrinolytic systems may be activated, probably due to enhanced proteinase activity. In acute renal failure, there is a release of granulocyte neutral proteinases. The plasma concentration of the elastase-alpha 1-proteinase inhibitor complex is simultaneously increased. Granulocytes of chronically uremic patients treated with diet or regular dialysis have a slightly to markedly reduced proteinase content as compared with normal controls. There is a dramatic rise of the plasma elastase alpha 1-proteinase inhibitor complex during hemodialysis treatment.
...
PMID:Proteolytic enzymes and catabolism: enhanced release of granulocyte proteinases in uremic intoxication and during hemodialysis. 637 17

In vitro findings suggest that alpha 2M is an important regulator of PDGF-stimulated fibroblast proliferation and chemotaxis. Native alpha 2M binds to PDGF and prevents PDGF from interacting with its receptor, but serves as an extracellular reservoir for the growth factor, which can be released over time in a controlled fashion to interact with the PDGF-alpha or -beta receptor. Methylamine-activated alpha 2M synergistically enhances PDGF-induced cell growth, whereas plasmin-activated alpha 2M inhibits PDGF-stimulated fibroblast proliferation. The reason for the difference in the effect of these two receptor-recognized alpha 2Ms is unknown. PDGF secreted by rat alveolar macrophages is bound to homologues of human alpha 2M and it has been suggested that PDGF action in the lung is tightly controlled during normal tissue remodeling. It is important to consider another regulator of PDGF termed SPARC (secreted protein, acidic and rich in cysteine), which inhibits the binding of PDGF-BB and -AB to cell-surface PDGF-beta receptors. SPARC could modulate PDGF activity during inflammation and tissue repair by limiting the availability of dimers containing the PDGF B chain. Future studies should address the relative importance of SPARC and alpha 2M in regulating PDGF-induced chemotaxis and proliferation. During inflammation or during the progression of fibroproliferative lung disease, the regulation of PDGF might be lost. For example, oxidative bursts from inflammatory cells (neutrophils and eosinophils) functionally inactivate alpha 2M. Thus, inhaled environmental insults (particles and oxidants) could perturb the normal growth regulatory signaling system between cells via the network that includes cytokines, alpha 2M, and proteinases.
...
PMID:Regulation of platelet-derived growth factor (PDGF) and alveolar macrophage-derived PDGF by alpha 2-macroglobulin. 752 5

Amyloid beta protein (beta/A4) is deposited in senile plaques of patients with Alzheimer's disease. This protein is derived from a larger membrane-associated protein, termed amyloid precursor protein (APP). The constitutive processing of APP occurs at the central portion of beta/A4, resulting in the release of large N-terminal peptides. We have purified these peptides from the culture medium of cDNA-transfected COS-1 cells. Some of the isoforms contain the Kunitz-type protease inhibitor (KPI) domain and strongly inhibit trypsin, chymotrypsin and plasmin, but do not inhibit kallikrein, prolyl endopeptidase or granzyme A. The peptides also do not inhibit cysteine proteases such as cathepsin B or calpain. Soluble APPs lacking the KPI domain fail to inhibit any of these proteases. The results indicate that the KPI domain in soluble APPs has protease inhibitory activity against certain serine proteases.
...
PMID:Inhibitory spectra of purified protease nexin-II and related proteins towards cellular proteinases. 790 50

The zoonotic hookworm, Ancylostoma caninum, probably induces human eosinophilic enteritis by inducing allergic responses to its secretions. This species is already known to secrete metalloproteinases, but in other parasites, cysteine proteinases are involved in pathogenesis. We studied somatic extracts of A. caninum adults and infective larvae and adult excretory/secretory (ES) antigens for cysteine proteinase activity using fluorogenic peptide substrates and by gelatin and fluorogenic substrate polyacrylamide gel electrophoresis. Proteolytic activity was observed against the cathepsins L and B-specific substrate Z-phe-arg-AMC, against the plasmin substrate Boc-val-leu-lys-AMC, and against gelatin. The Z-phe-arg-AMC-hydrolyzing activity in ES antigens and in adult extracts was enhanced up to 15-fold by the reducing agent dithiothreitol (DTT), but was totally blocked by specific inhibitors of cysteine proteinases, including the peptidyl diazomethyl ketone Z-phe-ala-CHN2,E-64, leupeptin, and N-ethylmaleimide. In a similar fashion, gelatinolytic activity in ES antigens detected using substrate gels was enhanced by the addition of reducing agents and inhibited by Z-phe-ala-CHN2 and E-64. The DTT-enhanced, Z-phe-arg-AMC-hydrolyzing activity in ES antigens was active over a wide pH range (pH 5-9). Similar cysteine proteinase activity to that detected in ES antigens was present in extracts of adult and infective larvae of A. caninum. Because the substrate Z-phe-arg-AMC was specifically hydrolyzed, and because this hydrolysis was totally blocked by cysteine proteinase-specific inhibitors, ES antigens and tissue extracts of A. caninum clearly possess cysteine proteinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Secretion of cysteine proteinase activity by the zoonotic hookworm Ancylostoma caninum. 794 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---