Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The following proteolytic enzymes were measured in muscles of control subjects and patients with muscular dystrophies and related neuromuscular diseases: an elastase-like enzyme, carboxypeptidase A, carboxypeptidase B and pyroglutamyl peptidase. 2. Elastase-like enzyme and carboxypeptidase B did not show significant alterations in various disease conditions that were examined. 3. Carboxypeptidase A was moderately elevated in dystrophic as well as other diseased muscles. 4. Pyroglutamyl peptidase was not markedly altered in any disease condition except that is was slightly lower in dystrophic muscles.
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PMID:Activity of some proteolytic enzymes in normal and dystrophic human muscle. 3 40

The enzyme carboxypeptidase A has been extensively studied and is thus a good candiate for chemical models and imitation. A model system was constructec which combined two of the three catalytic functional groups of the enzyme together with the appropriate substrate group, and cooperative effective catalysis was demonstrated. However, the mechanism which the model system used in enzyme-like conditions was unexpected, and this led to a study of the enzyme itself. Carboxypeptidase A was studied by examination of oxygen-18 exchange reactions and the ability of the enzyme to substitute only lytic agents, such as methanol, forthe water which is normally used. The result of these studies is proposed mechanism of action of this enzyme which accommodates the large amount of information already available, and which indicates that this enzyme uses a mechanism similar to that found in the model system. Approaches have also been made to an artificial enzyme which could hydrolyse amides. Cyclodextrin has been functionalized with two imidazole groups placed on opposite sides of the cavity. This material catalyses the hydrolysis of an amide, which binds to the cyclodextrin cavity and then is hydrolysed with the assistance of one imidazole in its basic form and the other one in its protonated form, acting together in a way reminiscent of the cooperation of some of the functional groups of hydrolytic enzymes.
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PMID:Studies on enzyme models and on the enzyme carboxypeptidase A. 24 79

Properties of carboxypeptidase A of cultured skin fibroblasts from control and cystic fibrosis patients were studied using alpha-N-carbobenzoxy-L-glutamyl-L-tyrosine as substrate. Carboxypeptidase A was inhibited by thiomersal, cyanide, iodoacetate and N-ethylmaleimide in a similar manner for control and cystic fibrosis fibroblasts. Both trypsin and dithiothreitol treatment activated the enzyme, but 1,10-phenanthroline inhibited only in the presence of dithiothreitol. Both Zn2+ and Co2+ reversed this inhibition. Trypsin treatment of carboxypeptidase A produced a form of the enzyme having a higher KM value for both control and cystic fibrosis fibroblasts. Dithiothreitol treatment of control fibroblasts resulted in a form with similar properties to the trypsin activated form, but cystic fibrosis fibroblasts yielded a variant form with even higher KM and Vmax values. Since other properties were similar, it seems likely that this difference reflected binding of a molecule to the enzyme rather than of a defect in the enzyme.
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PMID:Carboxypeptidase A activity of cultured skin fibroblasts and relationship to cystic fibrosis. 66 47

The activity of carboxypeptidase A [EC 3.4.12.2] was inhibited by 3-phenylpropionate derivatives (p-aminocinnamate, 3-p-aminophenylpropionate and 3-p-acetylaminophenylpropionate), and to investigate its use as a ligand for affinity chromatography 3-p-aminophenylpropionate was directely and indirectly coupled to Sepharose 4B. carboxypeptidase A was adsorbed only on 3-p-aminophenylpropionate bound to the gel through p-phenylenediamine as a spacer. Carboxypeptidase A from pancreas was purified by a combination of this affinity adsorbent and ion exchange chromatography. The purified carboxypeptidase A had a homogeneity similar to that of a commercial product, as judged by disc gel electrophoresis. The carboxypeptidase activity of Pronase was slightly retarded on the gel column, but could not be separated from its caseinolytic activity. Angiotensin I-converting enzyme [peptidyl dipeptidy hydrolase, EC 3.4.15.1] obtained from hog kidney cortex was not bound to the gel.
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PMID:Purification of carboxypeptidase A using Sepharose 4B-bound 3-phenylpropionate. 89 53

Undegraded 19-S thyroglobulin was purified from hog, ox, man, dog, sheep and rat thyroid glands. Sodium dodecylsulfate/ polyacrylamide gel electrophoresis of the reduced proteins showed that all are formed of peptide chains of molecular weight about 330000. Carboxypeptidase A digestion of porcine 19-S thyroglobulin released consecutively two moles of leucine and then two moles of serine, thus offering strong evidence in favour of the idea that the protein is formed of two identical chains. The same C-terminal amino acids were detected in sheep, ox, dog and man thyroglobulins. No N-terminal amino acid was found by appropriate chemical and enzymatic techniques. Porcine 27-S iodoprotein was shown by carboxypeptidase A analysis to be formed of four single-stranded 330000-Mr subunits identical to those constituting the 19-S protein. Identity, both qualitatively and quantitatively, of the peptides obtained by CNBr cleavage of the two proteins as shown by sodium dodecylsulfate/polyacrylamide gel electrophoresis has confirmed this conclusion. Since 19-S and 27-S thyroid iodoproteins are formed of two and four probably identical chains, they must be termed 19-S and 27-S thyroglobulins or alternatively thyroglobulin dimer and tetramer, respectively.
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PMID:Polypeptide chains of 19-S thyroglobulin from several mammalian species and of porcine 27-S iodoprotein. 91 16

Protein from hog which is recognized by human monoclonal antibody (HB4C5), generated from a patient with large cell lung carcinoma, was identified as carboxypeptidase A by comparison of the protein with carboxypeptidase A in enzymatic activity, immunologic reactivity, and amino acid sequence. Carboxypeptidase A activity was also found in human cancer tissue, and purified antigen from cancer tissue recognized by the antibody HB4C5 was reacted with rabbit anti-carboxypeptidase A serum, indicating that carboxypeptidase A is an antigen of HB4C5. Since large amounts of carboxypeptidase A can be obtained from porcine sources, a simple method for its purification was established. The fraction which was most reactive with HB4C5 was obtained from acetone powder of porcine pancreas by successive applications of water extraction, ammonium sulfate precipitation, trypsin treatment, and Mono Q column chromatography. Its apparent molecular weight was 40,000, according to SDS polyacrylamide gel electrophoresis. When the reactivity of IgG in sera with the purified carboxypeptidase A was measured, the detection rates for lung, ovary, larynx, uterus, and liver cancer were more than 50%, while the rates for stomach and breast cancer were around 30%, and pancreatic cancer, benign diseases, and normal controls were minimally detected.
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PMID:Serodiagnosis of cancer using porcine carboxypeptidase A as an animal antigen recognized by human monoclonal antibody HB4C5. 187 99

The "high-affinity Mn-binding site" in Mn-depleted photosystem II (PS II) membrane fragments isolated from Scenedesmus obliquus was examined by using the diphenylcarbazide (DPC)/Mn2+ non-competitive inhibition assay [Preston, C., & Seibert, M. (1991) Biochemistry (preceding paper in this issue)]. Different proteases were used to degrade lumenal surface protein segments from these PS II membranes, and a total of four independent high-affinity Mn-binding sites (ligands) were identified. Carboxypeptidase A, subtilisin, and Staphylococcus aureus V8 protease each degrade one of two high-affinity Mn-binding sites sensitive to the histidine chemical modifier diethyl pyrocarbonate (DEPC). However, sequential treatment experiments indicate that subtilisin degrades a DEPC-sensitive Mn-binding site that is different from the one degraded by the other two proteases. Trypsin also was found to degrade one of the DEPC-sensitive Mn-binding sites (that degraded by carboxypeptidase A and V8 protease). In addition, trypsin degrades one of two 1-ethyl-3-[(3-dimethylamino)propyl]carbodiimide (EDC) sensitive Mn-binding sites, but only in the absence of the 30-kDa extrinsic protein. Thus, the 30-kDa extrinsic protein associated with O2 evolution appears to protect the EDC-sensitive binding site from trypsin degradation. No protease has yet been identified that will degrade the trypsin-insensitive EDC-sensitive Mn-binding site. Under the conditions of the assay (high DPC concentration), more than three Mn per reaction center were found bound to the membrane with a KM of about 0.4 microM, as determined by direct metal analysis. This is consistent with the idea that each of the four high-affinity sites binds (or provides a ligand for) one of four Mn.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protease treatments of photosystem II membrane fragments reveal that there are four separate high-affinity Mn-binding sites. 191 48

Two peptides corresponding to the amino acid sequences 1-10 (N-terminal peptide) and 303-313 (C-terminal peptide) of the bovine heart mitochondrial phosphate carrier have been synthesized. After being coupled to ovalbumin, they were injected into rabbits to raise polyclonal antibodies. The specificity of the generated antibodies was tested by enzyme-linked immunosorbent assay (ELISA) and/or Western blot. Anti-N-terminal antibodies and anti-C-terminal antibodies exclusively reacted with the corresponding terminal peptide, they also reacted with the isolated phosphate carrier as well as with the phosphate carrier protein in mitochondrial lysates. Both anti-N-terminal and anti-C-terminal antibodies bound to freeze-thawed mitochondria, indicating that both termini of the membrane-bound phosphate carrier are exposed to the cytoplasmic side of the inner mitochondrial membrane. These immunological data were complemented with results concerning enzymatic cleavage of the membrane-bound phosphate carrier by carboxypeptidase A and by an arginine-specific endoprotease. Carboxypeptidase A markedly decreased the binding of anti-C-terminal antibodies to phosphate carrier in freeze-thawed mitochondria. Arg-endoprotease cleaved the phosphate carrier in inside-out submitochondrial particles, but not in right-side-out particles, yielding two fragments of similar apparent molecular weight (Mr approximately equal to 14.5K), which were immunodetected only by the anti-N-terminal antiserum, and a fragment of Mr approximately equal to 17K which was detected only by the anti-C-terminal antiserum. It appears, therefore, that Arg-endoprotease cleavage sites of the phosphate carrier are present only at the matrix side of the inner mitochondrial membrane, at Arg-140 and/or Arg-152.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transmembrane topography of the mitochondrial phosphate carrier explored by peptide-specific antibodies and enzymatic digestion. 203 64

Carboxypeptidase A and B were partially purified from the soluble fraction of longitudinal muscle layer (myenteric plexus) of bovine small intestine. The obtained carboxypeptidase A hydrolyzed [Met]enkephalin-Arg6-Phe7 and [Leu]enkephalin, but [Met]enkephalin was not a suitable substrate for the enzyme. The Km value of carboxypeptidase A for [Met]enkephalin-Arg6-Phe7 was 0.74 mM and that for [Leu]enkephalin was 0.44 mM. Intestinal carboxypeptidase B hydrolyzed [Met]enkephalin-Arg6, liberating [Met]enkephalin, and the Km value of the enzyme for [Met]enkephalin-Arg6 was 0347 mM.
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PMID:Separation of carboxypeptidase A and B from longitudinal muscle layer of bovine small intestine: their properties regarding hydrolysis of enkephalins and enkephalin-analogs. 345 45

The substrate specificity of rat mast cell protease I (RMCP I), a chymotrypsin-like serine protease localized in the secretory granules of mast cells, was compared to that of bovine alpha-chymotrypsin by using several peptide and protein substrates of known amino acid sequences. Although the overall specificities of the two proteases appeared similar, subtle but significant differences were observed. RMCP I was more prone than chymotrypsin to hydrolyze peptide bonds consisting of Leu-Xaa or two hydrophobic residues--e.g., Phe-Phe. Additionally, the hydrolysis of angiotensin I catalyzed by chymotrypsin, but not by RMCP I, resulted in the generation of angiotensin II as an intermediate product. In contrast to the solubilized enzyme, the RMCP I activity within the insoluble granules was completely stable for at least 2 months in suitable buffers at pH 8.0 or pH 7.2, at 4 degrees C. Carboxypeptidase A activity associated with isolated mast cell granules was completely inhibited by 10 mM o-phenanthroline. Polypeptides smaller than apomyoglobin (17,199 Da) were rapidly hydrolyzed by granule-bound RMCP I, whereas apomyoglobin and other larger proteins were not hydrolyzed. In contrast, the free protease readily hydrolyzed the larger proteins. Neither normal rat serum nor alpha 1-antitrypsin, both of which inhibited the activity of free RMCP I, was effective in inhibiting granule-associated RMCP I. The results indicate that granule-bound RMCP I is not released into solution from isolated secretory granules under physiological conditions of ionic strength and pH and that the granule structure limits the size of proteins that can be hydrolyzed by the protease.
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PMID:Substrate specificity of the chymotrypsin-like protease in secretory granules isolated from rat mast cells. 354 Sep 62


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