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:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the nanomolar enzyme and inhibitor concentration range, 1 mol of mucus proteinase inhibitor (MPI) inhibits 1 mol of neutrophil elastase, cathepsin G, trypsin, and chymotrypsin. In the micromolar concentration range, the enzyme:inhibitor binding stoichiometry is still 1:1 for elastase but shifts to 2:1 for the three other proteinases. These data could be confirmed by three nonenzymatic methods: (i) fluorescence anisotropy measurements of mixtures of proteinases with 5-dimethylaminonaphthalene-1-sulfonylated or fluoresceinylated MPI, (ii) absorption spectrocospy of fluorescein-MPI-proteinase complexes isolated by gel filtration, (iii) analytical ultracentrifugation which showed that the molecular mass of the MPI-chymotrypsin complex is 56 kDa, whereas that of the MPI-elastase complex is 39 kDa. The binary MPI-elastase complex is unable to inhibit trypsin or cathepsin G. On the other hand, 1 mol of elastase displaces 2 mol of trypsin or cathepsin G from their ternary complexes with MPI.
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PMID:The proteinase: mucus proteinase inhibitor binding stoichiometry. 153 27

The second, carboxyterminal domain of human mucus proteinase inhibitor (MPI) represents a strong antagonist of trypsin, chymotrypsin and leucocyte elastase. To modulate the inhibitory specificity and chemical stability of this domain, mutants have been prepared by site-directed mutagenesis of a cDNA fragment encoding for the carboxyterminal half of the inhibitor, followed by expression in E. coli. Inhibition assays with the purified recombinant domains revealed the possibility to create variants for potential pharmaceutical use.
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PMID:Expression and characterization of recombinant second domain variants of human mucus proteinase inhibitor (MPI). 180 41

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

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

Antileukoprotease or secretory leukocyte proteinase inhibitor is a potent serine proteinase inhibitor produced by exocrine glands of the human body. This monomeric protein (107 amino acids) comprises two homologous domains. It is generally thought that Leu19-Arg20-Tyr21 in the NH2-terminal domain represent the trypsin inhibitory activity, whereas Leu72-Met73-Leu74 in the COOH-domain represent the chymotrypsin and elastase inhibitory activity. Besides Met73, antileukoprotease contains three additional methionine residues all located in the COOH-terminal domain. Treatment of antileukoprotease with different amounts of methionine-selective reagents such as myeloperoxidase in the presence of H2O2 and Cl-, or cis-platinumdiammine dichloride resulted in a dose-dependent inactivation of all inhibitory activities, suggesting that methionine residues are involved in these activities. By using specific synthetic substrates, it was observed that elastase is able to displace trypsin from the inhibitor molecule, indicating that the trypsin and elastase inhibitory sites are located close to each other or at the same site. Incubation of antileukoprotease or its recombinant COOH-terminal domain with an antileukoprotease-specific monoclonal antibody (MoAb15) resulted in a strong selective increase of the trypsin inhibitory activity. The results presented reveal strong evidence that the inhibitory activities of antileukoprotease against trypsin, chymotrypsin and elastase are represented by its COOH-terminal domain, and that methionine residues are involved in interactions with these proteinases.
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PMID:Proteinase inhibitory activities of antileukoprotease are represented by its second COOH-terminal domain. 215 23

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

Human mucous secretions contain a proteinase inhibitor which is produced locally and inhibits, besides trypsin and chymotrypsin, granulocytic elastase and cathepsin G as well as mast cell chymase and tryptase. The various inhibitors isolated from different sources (bronchial mucus, parotid secretion, seminal plasma, cervical mucus, etc.) and named accordingly (bronchial mucus inhibitor, BMI; human seminal inhibitor I, HUSI-I; cervical mucus inhibitors, CUSI; antileukoprotease, ALP; secretory leukocyte protease inhibitor, SLPI) proved to be identical or derived from a mature inhibitory protein encoded by a single gene of the human genom. Therefore, this inhibitor should be named mucus proteinase inhibitor, MPI. Such a neutral terminus would help to avoid misleading interpretations of already published data and also of the biological role of this inhibitory protein because the MPI may serve several and different physiological functions.
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PMID:Human mucus proteinase inhibitor (human MPI). Human seminal inhibitor I (HUSI-I), antileukoprotease (ALP), secretory leukocyte protease inhibitor (SLPI). 306 Jan 47

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

Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally similar, low-molecular-weight antiproteases produced in the lung. We have developed a simple method for distinguishing the antiprotease activities of SLPI and elafin in lung lavage fluid from those of alpha 1-antitrypsin (alpha 1-AT) that is based on the resistance of the low-molecular-weight antiproteases to inactivation by cetyltrimethylammonium bromide. In a study of 23 healthy, nonsmoking volunteers, we found that the low-molecular-weight antiproteases accounted for 22 +/- 2% (mean +/- SEM, n = 23) of the total neutrophil elastase-inhibitory capacity of human bronchoalveolar lavage fluid (BALF). Elafin activity was below the limit of detection. SLPI activity (as measured by inhibition of alpha-chymotrypsin) accounted for 72 +/- 4% (mean +/- SEM, n = 23) of the low-molecular-weight antiprotease activity in BALF. Measurements of SLPI in the lavage fluid samples by enzyme-linked immunosorbent assay (ELISA) agreed closely with values obtained by measuring the activity of this inhibitor. The activity of the low-molecular-weight antiproteases decreased significantly (p < 0.05), from 9.0 +/- 0.8 to 7.0 +/- 0.6 pmol of neutrophil elastase inhibited per mL (mean +/- SEM, n = 23), following acute ozone exposure.
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PMID:Contribution of secretory leukocyte proteinase inhibitor to the antiprotease defense system of the peripheral lung: effect of ozone-induced acute inflammation. 758


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