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 peptidase that inactivated neurotensin by cleaving the peptide at the Pro10-Tyr11 bond, generating the biologically inactive fragments neurotensin(1-10) and neurotensin(11-13) was purified from whole rat ileum homogenate. The purified enzyme behaved as a 70-75-kDa monomer as determined by SDS-PAGE analysis in reducing or non-reducing conditions and gel permeation on Ultrogel AcA34. The peptidase was insensitive to thiol-blocking agents and acidic and serine protease inhibitors but could be strongly inhibited by 1,10-phenanthroline, EDTA, dithiothreitol and heavy metal ions such as zinc, copper and cobalt. Zinc was the only divalent cation able potently to reactivate the apoenzyme. This enzyme could be distinguished from endopeptidases EC 3.4.24.15 and EC 3.4.24.11, angiotensin-converting enzyme, proline endopeptidase, aminopeptidase and pyroglutamyl-peptide hydrolase since it was not affected by micromolar concentrations of their specific inhibitors. The peptidase displayed a high affinity for neurotensin (1.6 microM). Studies concerning the specificity of the enzyme towards the sequence of neurotensin established the following. (a) Neurotensin(9-13) was the shortest partial sequence that fully inhibited tritiated neurotensin degradation; shortening the C-terminal part of the neurotensin molecule led to inactive fragments. (b) Amidation of the C-terminal end of the peptide did not prevent the recognition by the peptidase. (c) There existed a strong stereospecificity of the peptidase for the residues in positions 8, 9 and 11 of the neurotensin molecule. (d) Pro-Xaa dipeptides (where Xaa represented aromatic or hydrophobic residues) were the most potent inhibitors of tritiated neurotensin degradation while all the Xaa-Pro dipeptides tested were totally ineffective. (e) The neurotensin-related peptides: neuromedin N, xenopsin and [Lys8-Asn9]neurotensin(8-13), as well as angiotensins I and II and dynorphins(1-8) and (1-13) were as potent as neurotensin in inhibiting [3H]neurotensin hydrolysis.
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PMID:Peripheral inactivation of neurotensin. Isolation and characterization of a metallopeptidase from rat ileum. 340 80

A peptidase that cleaved neurotensin at the Pro10-Tyr11 peptide bond, leading to the formation of neurotensin-(1-10) and neurotensin-(11-13), was purified nearly to homogeneity from rat brain synaptic membranes. The enzyme appeared to be monomeric with a molecular weight of about 70,000-75,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high pressure liquid chromatography filtration. Isoelectrofocusing indicated a pI of 5.9-6. The purified peptidase could be classified as a neutral metallopeptidase with respect to its sensitivity to pH and metal chelators. Thiol-blocking agents and acidic and serine protease inhibitors had no effect. Studies with specific peptidase inhibitors clearly indicated that the purified enzyme was distinct from enzymes capable of cleaving neurotensin at the Pro10-Tyr11 bond such as proline endopeptidase and endopeptidase 24-11. The enzyme was also distinct from other neurotensin-degrading peptidases such as angiotensin-converting enzyme and a recently purified rat brain soluble metalloendopeptidase. The peptidase displayed a high affinity for neurotensin (Km = 2.6 microM). Studies on its specificity revealed that neurotensin-(9-13) was the shortest neurotensin partial sequence that was able to fully inhibit [3H]neurotensin degradation. Shortening the C-terminal end of the neurotensin molecule as well as substitutions in positions 8, 9, and 11 by D-amino acids strongly decreased the inhibitory potency of neurotensin. Among 20 natural peptides, only angiotensin I and the neurotensin-related peptides (xenopsin and neuromedin N) were found as potent as unlabeled neurotensin.
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PMID:Purification and characterization of a novel neurotensin-degrading peptidase from rat brain synaptic membranes. 352 64

Several classes of proteolytic enzymes have been proposed to have a role in the processing of precursor forms of proproteins at paired basic amino acid residues. In higher eukaryotes, a single endopeptidase has yet to fulfill the necessary criteria as the physiologically relevant convertase. The observation of proalbumin circulating in a child with a bleeding disorder caused by an unusual alpha 1-antitrypsin mutation led to speculation that the presence of this alpha 1-antitrypsin mutant was inhibitory to the convertase. This provided an additional means of characterizing the processing enzyme. In this study the yeast KEX2 enzyme, a calcium-dependent thiol protease, was found to have all the properties expected for this processing enzyme. KEX2 correctly recognized and cleaved the prosequence in proalbumin. In addition, KEX2 was specifically inhibited by the mutant alpha 1-antitrypsin but not by other serine protease inhibitors.
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PMID:Yeast KEX2 protease has the properties of a human proalbumin converting enzyme. 354 Dec 6

A 19-kDa protein, present in low copy number in purified adenovirus type 2, has been characterized. Several criteria were used to establish that this protein is neither a degradation product of the known structural proteins of the virion nor a minor, unusually modified, form of protein VII. This 19-kDa protein, unlike other virion proteins, possesses alkali-resistant phosphoamino acids. Analysis by partial proteolysis indicated that it is related to a 23-kDa phosphoprotein present in H2ts-1 virions assembled in infected cells maintained at 39 degrees C. Affinity labeling with [3H]diisopropyl fluorophosphate showed that the 19-kDa protein contains the active site for a serine protease. We, therefore, conclude that the 19-kDa protein is the active form of the adenovirus-encoded endopeptidase, defined by the H2ts-1 mutation, and is synthesized as a 23-kDa precursor that appears to mature by autocatalysis.
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PMID:Adenovirus type 2 endopeptidase: an unusual phosphoprotein enzyme matured by autocatalysis. 354 35

A second collagenolytic serine protease has been isolated from the hepatopancreas of the fiddler crab, Uca pugilator. This enzyme cleaves the native triple helix of collagen under physiological conditions of pH, temperature, and ionic strength. In addition to its collagenolytic activity, the enzyme exhibits endopeptidase activity toward other polypeptides and small molecular weight synthetic substrates. The polypeptide bond specificity of this enzyme is similar to that of bovine trypsin as is its interaction with specific protease inhibitors. The amino-terminal sequence of this enzyme displays significant homology with other serine proteases, most notably with that of crayfish trypsin, and demonstrates that this enzyme is a member of the trypsin family of serine endopeptidases. The relatively unique action of this protease with regard to both collagenous and noncollagenous substrates has important implications concerning the specificity and mechanism of collagen degradation.
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PMID:A collagenolytic serine protease with trypsin-like specificity from the fiddler crab Uca pugilator. 633 26

The presence of an endopeptidase hydrolyzing succinyl trialanine-p-nitroanilide [Suc(Ala)3-pNA] to Suc(Ala)2 and Ala-pNA in human kidney and its partial characterization have been reported (Ishida et al. (1981) Biochem. Int. 3, 239-246). This neutral metallo-endopeptidase was separated into two fractions (A and B) on Sephacryl S-300 and fraction B was further purified to an electrophoretically pure state. The fraction B enzyme had a molecular weight of 100,000 and was inhibited by metal chelators such as EDTA, o-phenanthroline and phosphoramidon, but not by serine protease inhibitors. The enzyme was found to hydrolyze peptide bonds preferentially at the amino sides of hydrophobic amino acids such as Leu and Phe, when its specificity was studied using insulin B chain and angiotensin I. Fraction A seems to be a tetramer of fraction B, judging from its molecular weight, pI, substrate specificity and immunological properties.
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PMID:Purification and characterization of the neutral endopeptidase from human kidney. 635 93

Assay of solubilized dog pancreas microsomes revealed the presence of an endopeptidase which hydrolyzed the fluorogenic peptide substrate Suc-Ala-Ala-Phe-7-amino-4-methylcoumarin (AMC) between the alanine and phenylalanine positions. This activity was inhibited by phosphoramidon, 1,10-phenanthroline, and a number of synthetic inhibitors of thermolysin indicating that the enzyme is a zinc metallopeptidase. Endopeptidase activity was not inhibited by the serine protease inhibitors elastatinal, antipain, leupeptin, N-carbobenzyloxy-L-phenylethyl chloromethyl ketone, L-tosylamido-2-lysyethyl chloromethyl ketone, L-tosylamido-2-phenylethyl chloromethyl ketone, phenyl-methanesulfonyl fluoride, or low levels of chymostatin. The endopeptidase had a pH optimum between 7.0 and 7.5. The enzyme also hydrolyzed Suc-Ala-Ala-Ala-AMC and Suc-Ala-Gly-Ala-AMC in an analogous way to yield Ala-AMC. Thermolysis hydrolyzed Suc-Ala-Ala-Phe-AMC in an analogous way to the endopeptidase. However, thermolysin did not hydrolyze Suc-Ala-Ala-Ala-AMC or Suc-Ala-Gly-Ala-AMC, demonstrating that its substrate specificity differs from the endopeptidase.
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PMID:A zinc metalloendopeptidase associated with dog pancreatic membranes. 698 19

The effects of enzyme inhibitors on vasoactive intestinal peptide (VIP)-induced decreases in airway opening pressure (PaO) and VIP-like immunoreactivity (VIP-LI) recovery were studied in isolated tracheal superfused guinea pig lungs. In the absence of inhibitors, VIP 0.38 (95% CI 0.33-0.54) nmol/kg animal, resulted in a 50% decrease in PaO and 33% of a 1 nmol/kg VIP dose was recovered as intact VIP. In the presence of two combinations of enzyme inhibitors, SCH 32615 (S, 10 microM) and aprotinin (A, 500 tyrpsin inhibitor units [TIU]/kg) or S and soybean trypsin inhibitor (T, 500 TIU/kg), VIP caused a significantly greater decrease in PaO and greater quantities of VIP were recovered from lung effluent (both P < 0.001). The addition of captopril, (3 microM), leupeptin (4 microM), or bestatin (1 microM) failed to further increase pulmonary relaxation or recovery of VIP-LI. When given singly, A, T, and S did not augment the effects or recovery of VIP. The efficacy of S (a specific inhibitor of neutral endopeptidase [NEP]) and A and T (serine protease inhibitors) thus implicated NEP and at least one serine protease as primary modulators of VIP activity in the guinea pig lung. We sought to corroborate this finding by characterizing the predominant amino acid sites at which VIP is hydrolized in the lung. When [mono(125I)iodo-Tyr10]VIP was offered to the lung, in the presence and absence of the active inhibitors, cleavage products consistent with activity by NEP and a tryptic enzyme were recovered. These data demonstrate that NEP and a peptidase with an inhibitor profile and cleavage pattern compatible with a tryptic enzyme inactivate VIP in a physiologically competitive manner.
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PMID:Peptidase modulation of vasoactive intestinal peptide pulmonary relaxation in tracheal superfused guinea pig lungs. 767 3

A glycinin-digesting protease was purified from 4-h-imbibed soybean seeds to apparent homogeneity by a combination of DEAE-cellulose, gel filtration and Shodex IEC QA-824 chromatography. The purified soybean protease showed a single band on SDS-PAGE and degraded the carboxymethylated glycinin molecule at neutral or alkaline pH. The glycinin-digesting protease has an apparent molecular mass of 98 kilodaltons as estimated by SDS-PAGE under both reduced and non-reduced conditions. A peptidic substrate for the soybean protease was detected and purified from a tryptic digest of glycinin A5A4B3 complex; it corresponded to Ala(375)-Lys(381) of the B3 subunit. It was found that the protease could hydrolyze the peptide bond between Tyr(378) and Asn(389) of that peptide. The soybean protease was significantly inhibited by PMSF, indicating the endopeptidase is a serine protease. Moreover, the glycinin-digesting activity is also susceptible to EDTA and the inactivated enzyme could be restored by the addition of MnCl2, suggesting that Mn2+ is an important factor for the endopeptidase activity. To our knowledge, this is the first report of purification and characterization of a glycinin-digesting protease from soybean seeds.
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PMID:Purification and characterization of a CM-glycinin digesting protease from soybean seeds. 776 83

The complete amino acid sequence of duodenase, a new serine endopeptidase from bovine duodenal mucosa, has been determined. The sequence was reconstructed by the automated sequence analysis of the peptides obtained after cleavage with trypsin, Staphylococcus aureus V8 protease, cyanogen bromide and duodenase. The enzyme is composed of 226 amino acid residues yielding a molecular mass of 29.06 kDa. The presence of six cysteine residues and one potential sugar-chain-binding site at Asn50 was revealed. A predicted catalytic triade characteristic of the serine proteases was traced in the duodenase primary structure at the corresponding positions (His44, Asp87 and Ser181 in the sequence). Comparison of the sequence of duodenase with the other known primary structures of mammalian serine proteinases reveales the duodenase identity to granzymes from human and mice, human cathepsin G and mast cell chymases from rat, and gives an overall sequence identity of 47-55% with the mentioned enzymes. Alignment of the known serine protease and duodenase primary structures showed unique amino acid residues within the duodenase substrate-binding pocket at positions 189 (Asn) and 226 (Asp) (the bovine chymotrypsinogen A numbering). These results are discussed with respect to the relation between the duodenase unique residues within the primary specificity pocket S1 and the unusual dual specificity of the enzyme.
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PMID:Duodenase, a new serine protease of unusual specificity from bovine duodenal mucosa. Primary structure of the enzyme. 786 49


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