Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human mucus proteinase inhibitor is a two-domain protein which inactivates bovine trypsin and chymotrypsin, leukocyte elastase and cathepsin G. In order to localize the site(s) responsible for these inhibitory activities, the two domains were isolated after specific cleavage of the Asp49-Pro50 bond following mild acid treatment of the bronchial inhibitor. The carboxy-terminal domain was active against leukocyte elastase, trypsin and chymotrypsin whereas the amino-terminal domain, which contained a putative antitryptic active site, was devoid of activity. This implicates that, in the whole molecule, the inhibitory activity region is localized only in the carboxy-terminal domain.
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PMID:Separation of the two domains of human mucus proteinase inhibitor: inhibitory activity is only located in the carboxy-terminal domain. 193 Jan 99

Elastase-specific inhibitor (ESI) was purified from sputum of patients with chronic bronchitis and compared with mucus proteinase inhibitor (MPI, BrI) isolated, without the use of affinity chromatography on an enzyme, from non-purulent sputum of a patient with bronchial carcinoma. The N-terminal sequence of 27 residues of the latter was determined and showed serine as the only N-terminus. The partial N-terminal amino-acid sequence of ESI shows some homology with MPI, especially around the reactive site of MPI for human neutrophil elastase. This region could therefore be the reactive site of ESI. The thermodynamic and kinetic constants of the reactions of ESI with human neutrophil elastase and with porcine pancreatic elastase show that ESI is a fast-acting inhibitor.
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PMID:Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor. 203

Secretory leukocyte protease inhibitor (SLPI) is a two-domain protein that inhibits a wide range of proteases including chymotrypsin, leukocyte elastase, and trypsin. Based on its homology to other protease inhibitors and on x-ray crystallography of an SLPI-chymotrypsin complex it has been proposed that the elastase and chymotrypsin-inhibitory site is in the COOH-terminal domain and that the trypsin-inhibitory site is in the NH2-terminal domain. We have prepared muteins of SLPI by site-directed mutagenesis of a synthetic gene for the protein, followed by expression in Escherichia coli. The protease-inhibitory activities of these muteins indicate that leucine 72 in the COOH-terminal domain is at the inhibitory site for elastase and chymotrypsin. Unexpectedly, our measurements indicate that the trypsin-inhibitory site is not in the NH2-terminal domain. Instead they suggest that leucine 72 is also the inhibitory site for trypsin, even though the amino acid residues at the inhibitory sites of other trypsin inhibitors are almost always either lysine or arginine.
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PMID:Location of the protease-inhibitory region of secretory leukocyte protease inhibitor. 211 May 63

Human mucus proteinase inhibitor (MPI) consists of 107 amino acids arranged in two domains showing high homology to each other. This protein is an inhibitor of different serine proteinases including trypsin, chymotrypsin, leukocyte elastase and cathepsin G. On the basis of sequence comparisons it has been suggested that the first domain inhibits trypsin, whereas the second one was thought to be active against chymotrypsin and elastase. To prove the location of the different inhibitory activities gene fragments for both domains have been cloned separately and expressed in Escherichia coli. Inhibition assays with the isolated recombinant domains showed that the second domain is active against chymotrypsin, neutrophil elastase and trypsin, whereas for the first domain only a weak activity against trypsin could be detected. These results suggest that the inhibitory activities of the native molecule towards these three proteinases are all located in the second domain.
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PMID:The location of inhibitory specificities in human mucus proteinase inhibitor (MPI): separate expression of the COOH-terminal domain yields an active inhibitor of three different proteinases. 215 59

The present study was aimed at testing whether alpha 1-proteinase inhibitor-sufficient patients with lung emphysema or idiopathic spontaneous pneumothorax have an impaired antielastase protection at the lung alveolar level. We have collected bronchoalveolar lavage fluids (BALF) from 20 PIMM emphysematous patients (44 +/- 12 yr), 24 patients with pneumothorax but no radiologic evidence of emphysema (30 +/- 11 yr), 32 healthy subjects (27 +/- 6 yr), and 56 patients with sarcoidosis (30 +/- 11 yr). The BALF were assayed for immunoreactive albumin, alpha 1-proteinase inhibitor (alpha 1PI), leukocyte elastase-alpha 1PI complex (LE-alpha 1PI), and mucus proteinase inhibitor (MPI) as well as for porcine pancreatic elastase inhibitory capacity, a measure of active alpha 1PI. The healthy subjects and the patients with emphysema or pneumothorax had comparable levels of total and active alpha 1PI and total MPI. In contrast, the levels of LE-alpha 1PI complex were elevenfold higher in patients with emphysema than in normal subjects (p = 0.021) and tended to increase with the severity of the disease because they were negatively correlated with FEV1/FVC% (r = -0.55; 0.05 less than p less than 0.1). They did not vary with age in a population of patients with sarcoidosis (r = 0.03), suggesting that their eleven-fold increase in emphysematous patients is not related to the age of these subjects. Patients with pneumothorax had levels of LE-alpha 1PI complex that did not significantly differ from those of normal subjects (p = 0.24).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antielastase screen of the lower respiratory tract of alpha 1-proteinase inhibitor-sufficient patients with emphysema or pneumothorax. 232 50

Secretory leukocyte protease inhibitor (SLPI) and alpha-1-proteinase inhibitor (alpha-1-PI), both inhibitors of granulocyte elastase, were studied in nasal secretions from healthy persons and from patients with allergic rhinitis and common cold. SLPI and granulocyte elastase were found in all samples, while alpha-1-PI was lacking in several. In all three groups SLPI was found in an active form and in excess of granulocyte elastase, which thus was completely inhibited. The results indicate that SLPI is the main inhibitor in nasal secretions and that alpha-1-PI plays a minor role.
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PMID:Secretory leukocyte protease inhibitor in normal, allergic and virus induced nasal secretions. 278 Dec 19

Free radicals produced in a Fenton reaction (H202/Cu), modelling some xenobiotic and cell-mediated inflammatory affronts, efficiently inactivated the elastase-inhibitor eglin, but equally, human neutrophil elastase itself. Elastase activity was not regenerated from proteinase/inhibitor complexes during radical attack. Three different elastase inhibitors, eglin, secretory leukocyte proteinase inhibitor and alpha-1-proteinase inhibitor were all similarly sensitive to inactivation. Unlike certain oxidants which can selectively inactivate alpha-1-proteinase inhibitor, free radicals may influence comparably the availability of both proteinase inhibitors and their targets.
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PMID:Free radicals inactivate human neutrophil elastase and its inhibitors with comparable efficiency. 278 75

Human mucus proteinase inhibitor is a fast-acting inhibitor of human leucocyte elastase (EC 3.4.21.37) and forms a stable, complex with this enzyme. At physiological ionic strength and temperature and in the presence of 10 mg/ml albumin, the kinetic constants characterizing the interaction between elastase and the non-degraded inhibitor are: kass = 6.4.10(6) M-1.s-1, kdiss = 2.3.10(-3) s-1, Ki = 3.10(-10) M. The partially degraded inhibitor isolated by chymotrypsin-Sepharose chromatography inhibits elastase with similar efficiency, suggesting that if partial proteolysis of the inhibitor occurs in vivo, the latter may still act as a potent antielastase. Mucus proteinase inhibitor therefore plays a physiological antielastase function in upper respiratory tract secretions, since it inhibits elastase with a delay time of 150 ms and behaves like an irreversible inhibitor.
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PMID:Mucus proteinase inhibitor: a fast-acting inhibitor of leucocyte elastase. 292 15

An acid-stable, low molecular mass proteinase inhibitor, bronchial mucus proteinase inhibitor (BMPI), has been isolated from sputum and partially characterised. A single band with a modal molecular mass of 18 700 was observed following SDS-polyacrylamide gel electrophoresis. BMPI inhibited human leukocyte elastase, cathepsin G, trypsin and chymotrypsin, but not porcine pancreatic elastase. Although BMPI had a molecular mass close to the similarly isolated inhibitor of Girard et al. (Girard, F., Tournier, J.M., Polu, J.M. & Sadoul, P. (1980), Bull. Eur. Physiopathol. Respir. 16 (Suppl.) 237-245), and although it showed immunological cross reactivity to the low molecular mass inhibitor of Kramps et al. (Kramps, J.A., Franken, C., Meyer, C.J.L.M. & Dijkman, J.H. (1981) J. Histochem. Cytochem. 29, 712-719), it was found to have an amino-acid profile different to any previously described inhibitor. BMPI was detectable in bronchoalveolar lavage fluid collected from healthy and diseased human lungs. The median molar ratio of BMPI/alpha 1-proteinase inhibitor (alpha 1 PI) observed in these lavage samples was 0.7, which is generally higher than those derived from the data of other authors. This suggests that BMPI is a different protein to those previously described, although its exact relationship to other low molecular mass proteinase inhibitors remains to be determined.
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PMID:Acid-stable low molecular mass proteinase inhibitors in human lung lavage. 308 87

The dominating inhibitor of leukocyte elastase in human respiratory tract secretions is a low molecular mass inhibitor, designated antileukoproteinase. An equimolar antileukoproteinase-elastase complex was produced and subjected to gel filtration after differing time intervals and was found to be stable. On addition to human serum, however, elastase dissociated from antileukoproteinase and formed a complex with alpha 1-proteinase inhibitor. A small amount of elastase was also found bound to alpha 2-macroglobulin. Antileukoproteinase was capable of inhibiting elastase bound to alpha 2-macroglobulin. This inhibition was more complete and more rapid when the alpha 2-macroglobulin-elastase complex was in a molar ratio of 1:1 than in a ratio of 1:2.
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PMID:Studies on the interaction between leukocyte elastase, antileukoproteinase and the plasma proteinase inhibitors alpha 1-proteinase inhibitor and alpha 2-macroglobulin. 619 94


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