Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 93-residue peptide corresponding to the cytosolic domain of a human vesicle associated membrane protein (VAMP or synaptobrevin) has been prepared by solid-phase peptide synthesis in order to investigate the proteolytic activity of the tetanus toxin light chain (TeTx L chain). This protein has been recently reported to inactivate the neuronal rat synaptobrevin II by proteolysis. We show in this study that the synthetic human synaptobrevin II 1-93 (Syb II 1-93) as well as an N-terminus-shortened 69-residue peptide (Syb II 25-93) were cleaved selectively at the Gln76-Phe77 peptide bond by TeTx L chain while shorter peptides were not. A Michaelis constant Km = 192 +/- 2 microM and a catalytic constant kcat = 0.5 min-1 were found for the 93-residue peptide. A neutral optimum pH for the cleavage rate, an inhibition by preincubation of the toxin with well known nonspecific inhibitors of metallopeptidases as well as a zinc-dependent enzyme activity suggest that TeTx belongs to the zinc endopeptidase family. Moreover an activation by reducing agents and an inhibition by cysteine-modifying chemical reagents indicate a critical thiol dependency. Among several specific inhibitors of zinc endopeptidases tested, none could inhibit TeTx L chain even at high concentration. Structural studies by 600-MHz 1H-NMR showed that in water or dimethylsulfoxide the peptide Syb II 1-93 and shorter fragments did not present well defined conformations. Nevertheless protein-protein interactions have been shown for the peptides Syb II 1-93 and 25-93 but not for Syb II 51-93, a fragment not cleaved by TeTx L chain.
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PMID:Solid-phase synthesis, conformational analysis and in vitro cleavage of synthetic human synaptobrevin II 1-93 by tetanus toxin L chain. 820 Mar 42

A series of 13- and 14-membered ring lactam derivatives 9a,b, 10, 11, and 12a-c was prepared from L-cysteine. Compounds 9a,b and 12a,b were tested in vitro for inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) inhibition. The structure-activity profile of the series is discussed. Compound 9b, a 13-membered ring macrocyclic lactam, had an NEP IC50 of 18 nM and an ACEIC50 of 12 nM in vitro and showed dual plasma inhibition after intravenous or oral administration.
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PMID:Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors. 825 12

Multiple sequence alignment of the 12 adenovirus endopeptidases known to date identified a number of conserved residues which might be important for enzyme activity. Eleven mutants were created in the cloned gene by site-directed mutagenesis to identify the active site of this thiol endopeptidase. Analysis of the proteolytic activity in a crude system using viral precursor proteins, as well as in a purified system with activated proteinases using a new chromophoric octapeptide substrate, yielded results consistent with Cys-104 and His-54 being two members of the active site. This result was confirmed by the carboxymethylation of the reactive Cys-104 and its prevention by the active-thiol-specific agent E64. Although Cys-122 and Cys-126 were also reactive cysteines, mutation of these residues did not affect enzyme activity. Replacement of the active-site Cys-104 by serine converted the enzyme into a serine-like proteinase, sensitive to serine proteinase inhibitors. The absence of homology to other proteinases, particularly at the active-site cysteine, coupled with the requirement for activation by a substrate cleavage fragment, indicates that the adenovirus endoproteinase may represent a new subclass of cysteine proteinases.
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PMID:Identification of active-site residues of the adenovirus endopeptidase. 830 55

The action of neuropeptides at the synapse is terminated through enzymatic degradation by membrane-bound proteases. We defined and purified membrane-bound proteases functioning at the initial stage of degradation of four neuropeptides. 1. Substance P-degrading endopeptidases isolated from the rat brain and pig striatum showed similar properties to those of endopeptidase-24.16 (neurolysin) except for cleavage sites of substance P. 2. LHRH fragment (1-5)-generating endopeptidases isolated from the neuroblastoma cells and rat brain showed similar properties to those of endopeptidase-24.15 (thimet oligopeptidase). 3. One of two dynorphin-degrading cysteine proteases isolated from neuroblastoma cells showed strict specificity toward the Arg-Arg residues. 4. Endopeptidase-24.11 (neprilysin) isolated from the rat brain was identified as a somatostatin-degrading enzyme.
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PMID:[Membrane-bound proteases involved in neuropeptide degradation in the brain]. 836 28

In the search for the endopeptidase gene, short segments of genomic DNA were sequenced from the avian adenovirus type 1 (CELO) HindIII C and G fragments. On the basis of homology of the translated segments to Ad2 proteins, the genes for hexon, endopeptidase, DNA-binding protein, and 100K protein were mapped in that order between map units 41 and 63. The endopeptidase gene was encoded within a 900 nucleotide segment extending leftward from the EcoRI site at coordinate 50. The predicted Aavl endopeptidase consists of 206 residues of which 66% are similar to the sequence of the human Ad2 enzyme. Alignment of the known endopeptidase sequences identifies a single conserved histidine (H54) and two conserved cysteine residues (C104, C122) as likely candidates for the catalytic site of this thiol proteinase.
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PMID:Organization of the avian adenovirus genome and the structure of its endopeptidase. 839 24

Asparaginyl endopeptidase was highly purified from mature seeds of the jack bean (Canavalia ensiformis). The final enzyme preparation showed a single peak in high-performance liquid chromatography on a reversed-phase column, and the material in the peak gave the following NH2-terminal amino acid sequence on Edman degradation for 25 cycles: H-Glu-Val-Gly-Thr-Arg-Trp-Ala-Val-Leu-Val-Ala-Gly-Ser-Asn-Gly-Tyr-Gly-Asn-Tyr- Arg-His-Gln-Ala-Asp-Val-. Behavior of the enzyme toward various protease inhibitors suggested that it belongs to a family of cysteine proteases. Strict substrate specificity of this enzyme was verified by the use of 14 polypeptide substrates including those derived from proteins. Almost all the peptide bonds on the carboxyl side of Asn residues were susceptible to the enzyme. The exceptions were cases where the residue was at the NH2 terminus or the second position from the NH2 terminus of substrates and where it was N-glycosylated Asn. Peptide bonds on the carboxyl side of any other amino acid residues were not cleaved. These properties promise the high utility of this novel endopeptidase in protein sequence analysis. Identity of jack bean asparaginyl endopeptidase with a processing enzyme responsible for maturation of concanavalin A from its precursor is also discussed.
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PMID:Asparaginyl endopeptidase of jack bean seeds. Purification, characterization, and high utility in protein sequence analysis. 842 28

Cysteine endopeptidase inactivators were tested as inhibitors of interleukin 1-stimulated proteoglycan release from bovine nasal septum cartilage explants. Hydrophilic inactivators showed no inhibition at concentrations up to 100 microM. In contrast, lipophilic inactivators gave significant inhibition, which was both reversible and specific. No effects on interleukin 1 signal transduction were detected, but rates of proteoglycan synthesis were apparently increased. Our results suggest that one or more of the lysosomal cathepsins B, L and S mediate cytokine-stimulated proteoglycan degradation, and the turnover of newly synthesized proteoglycan, but that effective inhibitors must pass through membranes.
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PMID:The inhibition of interleukin 1-stimulated cartilage proteoglycan degradation by cysteine endopeptidase inactivators. 845 27

Proteolytic activity and activity of endogenous inhibitors of endopeptidases (using chymotrypsin and papain) were studied in the myocardium of rats with experimental ischemia during an acute phase (60 min) and within 5 days after ligation of the left descending coronary artery; effects of the beta-adrenoblocking agent propranolol and the calcium antagonist verapamil on these activities was also studied. During the acute phase of ischemia, the activity of acid proteases was increased by 30%, that of Ca(2+)-activated neutral proteases by 15-20%. At the same time, the activity of serine proteases inhibitors was decreased while the activity of thiol protease inhibitors was increased. Within 5 days of coronary artery occlusion, Lysosomal thiol-dependent endopeptidases were activated in the myocardium; a considerably higher activity of the inhibitors of serine- and cysteine-containing endopeptidases was detected. The cardioactive drugs propranolol and verapamil affected selectively both endopeptidase activity and their inhibitors.
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PMID:[Activity of proteolytic enzymes and their inhibitors in experimental myocardial ischemia]. 849 66

Der f II is a major mite allergen consisting of 129 amino acid residues. Der f II contains six cysteine residues, suggesting the existence of three disulfide bonds which would stabilize this small protein. As the first step in revealing the relationship between the structure and the allergenic property of Der f II, the formation of disulfide bonds was examined. Der f II purified from Dermatophagoides farinae was treated with lysyl-endopeptidase or proline-specific endopeptidase, and the peptide fragments thus generated were separated by reverse phase high performance liquid chromatography. Determination of the amino acid sequence of each peptide collected in this way proved the existence of three disulfide bonds between Cys8 and Cys119, Cys21 and Cys27, and Cys73 and Cys78.
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PMID:Determination of three disulfide bonds in a major house dust mite allergen, Der f II. 850 52

To identify oncosphere excretory/secretory peptidases, Taenia saginata adult worms were collected from 3 patients. Eggs were hatched and activated in vitro and oncospheres cultured in vitro. The culture medium from the oncospheres was assayed with peptide substrates coupled to 7-amino-4-trifluoromethyl coumarin (AFC), and free AFC was detected fluorometrically. The endopeptidase substrates Z-Phe-Arg-AFC and Z-Arg-AFC as well as the aminopeptidase substrate Arg-AFC were hydrolyzed when incubated with spent media from the oncospheres compared to control culture medium removed prior to incubation. Hydrolysis of Z-Phe-Arg-AFC was inhibited 78% by preincubation of the medium with the serine proteinase inhibitor Phenylmethylsulfonyl fluoride. Endopeptidase activity was partially enhanced in the presence of exogenous thiols and partially inhibited with the cysteine proteinase inhibitor E-64, suggesting the presence of both serine and cysteine endopeptidases. No significant inhibition was noted with pepstatin or phenanthroline. The peptidase activities detected with Z-Phe-Arg-AFC and Arg-AFC were separated by gel-filtration fast protein liquid chromatography and eluted at volumes corresponding to molecular weights of 18 and 30 kDa, respectively. These data demonstrate that T. saginata oncospheres produce excretory/secretory peptidases, including serine and cysteine endopeptidases and an aminopeptidase. These enzymes may play a role in invasion of the intestinal mucosa of the intermediate host.
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PMID:Taenia saginata oncosphere excretory/secretory peptidases. 862 4


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