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:3.4.21.37 (neutrophil elastase)
4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of human plasma alpha-1-antichymotrypsin with serine proteinases from different tissues has been investigated. The protein was found to form stable complexes with pancreatic chymotrypsin, leukocyte cathepsin G, and mast cell chymotrypsin. No inhibition of pancreatic trypsin or leukocyte elastase could be demonstrated. With mixtures containing both alpha-1-antichymotrypsin and alpha-1-proteinase inhibitor, it was found that the former preferentially inactivated leukocyte cathepsin G, while the latter showed a strong preference for pancreatic chymotrypsin. However, leukocyte elastase was specifically inactivated by alpha-1-proteinase inhibitor even in 1:1 mixtures with chymotrypsin. All of these results taken together suggest that one of the primary functions of alpha-1-antichymotrypsin is to inactivate leukocyte cathepsin G, while alpha-1-proteinase inhibitor controls the activity of other serine proteinases, particularly leukocyte elastase.
...
PMID:Human alpha-1-antichymotrypsin: interaction with chymotrypsin-like proteinases. 72 23

1. The elastase of human spleen was shown to exhibit endopeptidase activity against azo-casein and elastin. 2. Activity against several synthetic substrates was detected, and benzyloxycarbonyl-L-alanine 2-naphthyl ester was found to be a good substrate for routine use. 3. The enzyme showed a broad pH optimum in the range of 8.2-9.2 against azo-casein and the synthetic substrate. 4. The effect of inhibitors on the spleen elastase showed it to be a serine proteinase with a specificity similar to that of porcine pancreatic elastase. 5. Specific antisera were raised against the enzyme, and it was shown to be immunologically identical with the lysosomal elastase of human neutrophil leucocytes.
...
PMID:Human lysosomal elastase. Catalytic and immunological properties. 93 78

A chymotrypsin-like enzyme (EC 3.4.21.-) was purified from granules of human neutrophiles (polymorphonuclear leucocytes). The isolation procedure included differential salt extractions of the granules followed by affinity chromatography on 4-phenylbutylamine-Affi-Gel. This rapid purification method resulted in obtaining pure enzyme in relatively high yield in short time. The purified granulocyte chymotrypsin-like enzyme has a minimum Mr of 22 378, calculated from its amino acid composition. The Mr value obtained by sodium dodecyl sulphate gel electrophoresis was 20 000-23 000. The enzyme did not react with antibodies which are monospecific to granulocyte elastase. The granulocyte chymotrypsin-like enzyme was inactivated by Dip-F and by the chloromethyl ketone derivatives Z-PheCH2Cl and Z-(Gly)2-PheCH2Cl but not by Tos-PheCH2Cl. It therefore appears that the enzyme has serine and histidine side chains in its active site, like pancreatic chymotrypsin. The granulocyte enzyme substrate specificity is similar to that of pac-Tyr-Nan and Ac-Phe-1-ONap. It also has an intrinsic weak hydrolytic activity towards some classical elastase substrates such as Boc-Ala-ONp and Ac-DL-Ala-1-ONap. The granulocyte enzyme is inhibited by human serum and by human alpha1-antitrypsin. Its affinity for alpha1-antitrypsin is weaker than that of granulocyte elastase for the same inhibitor. The enzyme is stable at neutral pH at 37 degrees C, but unstable at pH 3.5 and at elevated temperature.
...
PMID:A rapid method for purification of human granulocyte cationic neutral proteases: purification and characterization of human granulocyte chymotrypsin-like enzyme. 108 Oct 3

Serine proteinase inhibitory proteins (SPIs) were extracted from human disc tissues using 2 M GuHCl and subjected to CsCl density gradient ultracentrifugation. The SPIs recovered in the low buoyant density fractions (rho < or = 1.35 g/ml) were purified by a combination of gel-permeation, ion-exchange, trypsin affinity, and reverse-phase high performance chromatographies. Characterisation of the major disc SPI by polyacrylamide gel electrophoresis, isoelectric focussing, enzyme inhibition and pH stability studies indicated that this small molecular weight (12-14 kDa), highly basic (pI > 9.5), acid-stable but alkaline-labile protein possessed potent inhibitory activity against bovine pancreatic trypsin and chymotrypsin, and human leukocyte elastase and cathepsin G. Two-major and two-minor low molecular weight cationic SPI species were identified by reverse-phase HPLC. The predominant species was identical to a human articular cartilage SPI sharing amino terminal sequence homology with the mucus proteinase inhibitors (MPIs). It also cross-reacted with an antiserum to the MPIs and behaved identically to secretory leucocyte proteinase inhibitor (SLPI) when examined by reverse phase HPLC, and SDS PAGE. A higher molecular weight (54 kDa), anionic (pI approximately 4.6) SPI was also purified and identified as alpha 1-proteinase inhibitor (alpha 1-PI). Quantification of alpha 1-PI and the small molecular weight cationic disc inhibitors indicated that the latter were depleted in morphologically degenerate disc tissues while levels of alpha 1-PI were somewhat higher although a large proportion of the alpha 1-PI was inactive. A depletion of total SPI levels was evident overall in degenerate discs suggesting a functional role for these inhibitory proteins in the maintenance of IVD matrix homeostasis.
...
PMID:The serine proteinase inhibitory proteins of the human intervertebral disc: their isolation, characterization and variation with ageing and degeneration. 128 14

We investigated the effect of ulinastatin, a candidate anti-osteoarthritic drug, in comparison with indomethacin and triamcinolone, two well-known drugs for osteoarthritis, on IL-1 production by monocytes, proteoglycan synthesis by chondrocytes and superoxide generation by leukocytes. Ulinastatin, a glycoprotein purified from human urine, suppressed both the IL-1 production and the IL-1 induced reduction of proteoglycan synthesis. In addition, ulinastatin inhibited superoxide generation. These actions of ulinastatin seemed to be related to its inhibitory actions against serine proteases such as trypsin, alpha-chymotrypsin, plasmin, leukocyte elastase and leukocyte cathepsin G. Triamcinolone suppressed the IL-1 production more potently than ulinastatin and it also suppressed the IL-1 induced reduction of proteoglycan synthesis. Triamcinolone alone, however, reduced the proteoglycan synthesis, and it did not affect the superoxide generation. In contrast, indomethacin had no effect on proteoglycan synthesis and superoxide generation, although it accelerated the IL-1 production. These results indicate that these three drugs have different mechanisms of action on the factors involved in the pathogenesis of osteoarthritis. Since ulinastatin has broad actions, which are considered to be beneficial for preventing some process of osteoarthritic pathogenesis, ulinastatin is expected to be an useful drug for the treatment of osteoarthritis.
...
PMID:[Mechanism of the anti-osteoarthritic action of ulinastatin in comparison with those of indomethacin and triamcinolone]. 131 79

The association rate constants (kon) of human, ovine, and baboon neutrophil elastase with two recombinant serine proteinase inhibitors (Eglin c, secretory leukocyte proteinase inhibitor) were compared. The association rate constant of sheep leukocyte elastase (SLE) with Eglin c is about 100 times lower (kon = 2.2 x 10(5) M-1s-1) than that of human elastase (kon = 2.4 x 10(7) M-1s-1). Baboon elastase, however, is as effectively blocked with Eglin c (kon = 2.5 x 10(7) M-1s-1) as human elastase. Secretory leukocyte proteinase inhibitor (SLPI) blocks the elastase of all three species with high efficiency; baboon elastase shows the highest association rate constant (kon = 5.6 x 10(7) M-1s-1) followed by human elastase (kon = 4.1 x 10(7) M-1s-1) and finally sheep elastase (kon = 1.2 x 10(7) M-1s-1). These findings demonstrate marked differences in the inhibition kinetic properties of ovine and human elastase. Concerning a future clinical application of proteinase inhibitors, the baboon seems a more suitable model than sheep to evaluate the effects of Eglin c and SLPI, since both inhibitors block baboon and human elastase with comparable efficiency.
...
PMID:Inhibition of human, ovine, and baboon neutrophil elastase with Eglin c and secretory leukocyte proteinase inhibitor. 135 Jan 99

Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, normally protects the upper airway epithelial surface from attack by neutrophil elastase (NE). In the context that a variety of inflammatory lung diseases are characterized by large neutrophil burdens with resultant high levels of NE in the lung, recombinant SLPI (rSLPI), a molecule identical to natural SLPI, may be an effective means to augment the anti-NE protective screen of the lung. To determine whether intravenous rSLPI will augment respiratory tract and epithelial surface levels of SLPI and anti-NE capacity, rSLPI was administered intravenously to sheep and SLPI levels were quantified in plasma, lung lymph (as a measure of lung interstitial levels), lung epithelial lining fluid (ELF), and urine. rSLPI (1 g) was administered over 10 min, and after 30 min plasma levels of SLPI were 8 microM and decreased with a half-life of 1.8 h. Lymph SLPI levels paralleled the plasma levels: 4 h after infusion the lymph-to-plasma ratio was 0.8. ELF SLPI levels paralleled the lymph levels: 4 h after infusion the ELF-to-lymph ratio was 0.3. Western analysis demonstrated intact SLPI in lymph and ELF, and functional analysis showed increases in lymph and ELF anti-NE capacity that paralleled the levels of SLPI. As might be expected from a protein with a molecular mass of 12 kDa, urine excretion was high, with 20% of the SLPI excreted over 5 h. However, if the rate of infusion was slowed, SLPI excretion decreased significantly, with a 3-h infusion associated with 9% excretion and a 12-h infusion associated with less than 0.2% excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Intravenous recombinant secretory leukoprotease inhibitor augments antineutrophil elastase defense. 135 69

The cell-free haemolymph of the mollusc Octopus vulgaris inhibited the proteolytic activity of the thermolysin against the high-molecular-mass substrate hide powder azure. The purified inhibitor was a glycoprotein composed of two identical 180 kDa disulphide-linked subunits. In addition to the inhibition of the metalloproteinase thermolysin, the protein inhibited the serine proteinases human neutrophil elastase, pig pancreatic elastase, bovine chymotrypsin, bovine trypsin and the cysteine proteinase papain. A fraction of the proteinase-inhibitor complex resisted dissociation after denaturation indicating that some of the proteinase molecules became covalently bound. The nucleophile beta-aminopropionitrile decreased the covalent binding of proteinases to the Octopus vulgaris protein, suggesting that this interaction is mediated by an internal thiol ester; the reactivity and the amino acid sequence flanking the reactive residues of the putative thiol ester were consistent with this hypothesis. Bound trypsin remained active against the low-molecular-mass chromatogenic substrate H-D-Pro-Phe-Arg p-nitroanilide and was protected from inhibition by active-site-directed protein inhibitors of trypsin; however, the bound trypsin was readily inhibited by small synthetic inhibitors. This indicates that the inhibition of proteinases is accomplished by steric hindrance. The proteinase-inhibitory activity of this protein is characteristic of inhibition by mammalian alpha-macroglobulins and the presence of a putative thiol ester suggests that the Octopus vulgaris proteinase inhibitor is a homologue of human alpha 2-macroglobulin.
...
PMID:Purification and characterization of an alpha-macroglobulin proteinase inhibitor from the mollusc Octopus vulgaris. 137 44

Proteinase-3 (PR-3) is a neutral serine proteinase present in the azurophil granules of human polymorphonuclear leukocytes. It degrades a variety of extracellular matrix proteins including elastin in vitro and causes emphysema when administered by tracheal insufflation to hamsters. It is identical to the target autoantigen (c-ANCA) associated with Wegener's granulomatosis and to myeloblastin, a serine proteinase first identified in HL-60 leukemia cells. In this study, the gene encoding PR-3 was cloned and sequenced. The gene spans approximately 6.5 kilobase pairs and consists of five exons and four introns. The genomic organization of PR-3 is similar to that of the other serine proteinases expressed in hemopoietic cells. Each residue of the catalytic triad of PR-3 is located on a separate exon, and the positions of the residues within the exons are similar to those in human leukocyte elastase and cathepsin G. The phase and placement of the introns in the PR-3 gene are also similar to those in human leukocyte elastase and cathepsin G. The 400-base pair (bp) 5'-flanking sequence of the PR-3 gene contains a TATA box at position 379. There is no CAAT box promoter element. The 3'-untranslated region is 200 bp, extending from a TGA stop codon to the site of polyadenylation 10 bp after the canonical AATAAA signal. Amplification of PR-3 from a human/hamster hybrid cell line localizes the gene to human chromosome 19. Evidence from Northern analysis suggests that PR-3 expression is primarily confined to the promyelocytic/myelocytic stage of bone marrow development.
...
PMID:Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen. 140 Apr 30

alpha 1-Antitrypsin (AAT) is a potent fluid-phase inhibitor of serine proteases. It forms a tightly bound, stoichiometric complex with these enzymes and is inactivated by cleavage within its reactive center. Evidence is here presented, that the 44-residue C-terminal fragment of AAT, termed SPAAT (short peptide from AAT), is found in human tissue, where it is apparently bound to the extracellular matrix (ECM). The identity of SPAAT was established by amino acid sequence analysis through its 40 N-terminal residues. Placental SPAAT inhibits chymotrypsin, human neutrophil elastase (HNE) and pancreatic elastase, but has no effect on trypsin. Unlike AAT, both placental and chemically-synthesized SPAAT are reversible, competitive inhibitors of chymotrypsin with Kl's of 0.92 and 7.5 microM, respectively. Both AAT and placental SPAAT also bind to diisopropyl fluorophosphate (DFP)-treated HNE as well as cathepsin G. SPAAT may therefore play an important role in the protection of ECM proteins, such as elastin, proteoglycans (PG) and/or collagen, from inappropriate attack by serine proteases.
...
PMID:Isolation and serine protease inhibitory activity of the 44-residue, C-terminal fragment of alpha 1-antitrypsin from human placenta. 140 56


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

---