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:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of recent reports that suggested that proteasomes, via an ATP-dependent process, become integral components of a '26 S' complex possessing 3-carboxypropionyl-Leu-Leu-Val-Tyr 4-methylcoumarin-7-ylamide-hydrolysing activity, we have investigated the molecular interaction of proteasomes in ATP-stabilized fraction II (proteins absorbed on DEAE-matrix and eluted with 0.5 M-KCl) of rabbit reticulocytes and mouse liver. Analysis of the various extracts by (NH4)2SO4 fractionation, velocity-gradient centrifugation, non-denaturing PAGE and SDS/PAGE and immunoblotting with proteasome-specific antisera failed to identify the proteasome as part of a higher-molecular-mass '26 S' multienzyme complex. In all instances proteasomes are identified in their 'free' 650 kDa '20 S' form. In addition to the proteasome and independent of the presence of MgATP, we isolated a high-molecular-mass proteinase whose electrophoretic migration behaviour and sedimentation rate correspond to that of the previously described '26 S' proteinase. This '26 S' proteinase possesses a strong 3-carboxypropionyl-Leu-Leu-Val-Tyr 4-methylcoumarin-7-ylamide-hydrolysing activity and is composed of several non-identical polypeptides in the molecular-mass range 20-150 kDa. Despite its similarity to proteasomal enzyme activity, protein analysis and immunoblotting experiments demonstrate that neither the intact proteasome nor subunits thereof are components of the '26 S' proteinase complex.
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PMID:Molecular interaction of the proteasome (multicatalytic proteinase). Evidence that the proteasome is not a constituent of the '26 S' multienzyme complex. 174 50

Two metalloendopeptidases, designated as Streptomyces griseus metalloendopeptidases I and II (SGMPI and SGMPII), were isolated from a commercial Pronase P by a method including affinity chromatography on carbobenzoxy-L-alaninyl-triethylenetetraminyl-Sepharose (Z-Ala-T-Sepharose). The two enzymes differed from each other in behavior on ion-exchange chromatography but showed the same amino-terminal sequence at least up to the 20th residue. Their molecular weights were both estimated to be 37,000 by SDS-polyacrylamide gel electrophoresis. Elemental and amino acid composition analyses indicated that both of them contained about 1 g atom of zinc and one cystine residue per mol of protein. Cleavage specificities of the two enzymes toward synthetic peptide-substrates were very similar to those observed with thermolysin. EDTA, o-phenanthroline, and phosphoramidon strongly inhibited these enzymes, while typical serine-protease inhibitors and cysteine-protease inhibitors had no effect. The findings clearly indicate that SGMPI and SGMPII can be classified into the family of zinc-endopeptidases. It was unexpectedly found, however, that these metalloendopeptidases were strongly inhibited by protein serine-protease inhibitors produced by Streptomycetes, such as Streptomyces subtilisin inhibitor (SSI), alkaline protease inhibitor-2c' (API-2c'), and plasminostreptin (PS).
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PMID:Purification and characterization of Streptomyces griseus metalloendopeptidases I and II. 176 59

We have purified the multicatalytic proteinase from the nucleus and cytoplasm of chicken red blood cells. Both enzymes have an Mr of 700 kDa and can be separated into 8-10 bands (22-32 kDa) on 1D-SDS-PAGE.
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PMID:Purification of the multicatalytic proteinase from the nucleus and cytoplasm of chicken red blood cells. 180 12

The multicatalytic proteinase (MCP) is a high-molecular-mass non-lysosomal proteinase that gives rise to a characteristic pattern of bands of molecular mass 22-34 kDa on SDS/PAGE gels. Isoelectric-focusing gels of the enzyme purified from rat liver show 16 bands with isoelectric points in the range of pH 5-8.5. Two-dimensional PAGE gels reveal that there are more than the previously reported 13 polypeptides associated with the MCP from rat liver and show a pattern of 15-20 major spots and several minor ones, similar to that of MCP isolated from some other sources. Possible relationships between the different polypeptides were investigated by immunoblot analysis of electrophoretically purified proteinase subunits with affinity-purified subunit-specific antibodies as well as antibodies raised against individual denatured subunits of the complex. The results demonstrate that many of the major polypeptide components of the MCP complex are antigenically distinct. Moreover comparison of immunoreactive material in crude cell extracts with that in purified MCP preparations has shown that the polypeptides are not derived from a smaller number of higher-molecular-mass subunits. Also, individual subunits have the same apparent molecular mass in a variety of rat tissues, suggesting close similarity between MCPs of different tissues. The highest concentrations of MCP subunits occur in liver and kidney. Gel-filtration analysis of crude extracts has demonstrated that MCP polypeptides are also associated with a higher-molecular-mass complex, which may be the 26 S proteinase that has been implicated in the degradation of ubiquitin-protein conjugates.
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PMID:Properties of subunits of the multicatalytic proteinase complex revealed by the use of subunit-specific antibodies. 188 28

Membrane cofactor protein (MCP; CD46) is a widely distributed C3b/C4b-binding cell surface glycoprotein which serves as an inhibitor of complement activation on host cells. The protein has been purified, multiple cDNAs cloned and sequenced, and the genomic organization determined. MCP belongs to a family known as the regulators of complement activation (RCA) gene cluster. The RCA members are related structurally [possess approximately 60 amino acid repeating motifs termed short consensus repeats (SCR)], functionally (bind C3b/C4b), and genetically (genes are tightly clustered on chromosome 1 at q3.2). Beginning at its amino-terminus, MCP is composed of four SCRs, a ser/thr/pro-enriched region, an area of undefined function, a transmembrane hydrophobic domain, a cytoplasmic anchor and cytoplasmic tail. On SDS-PAGE, MCP migrates as two broad forms with Mrs of 59,000-68,000 and 51,000-58,000. The quantity of each form expressed is inherited in an autosomal codominant fashion. This structural heterogeneity is partly explained by the expression of multiple cDNA/protein isoforms that arise by alternative splicing of ser/thr/pro-rich exons (sites of heavy O-glycosylation) and of cytoplasmic tails. This protein is of interest to immunologists and clinicians because of its role in regulation of the complement pathways and, therefore, inflammation in immune complex-mediated syndromes; to reproductive immunologists on account of its expression on sperm and at the maternal-fetal interface; and to tumor immunologists because of its high expression on malignant cells. The availability of monoclonal and polyclonal antibodies and molecular probes will be helpful in addressing questions about the biology of MCP in these and other areas.
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PMID:Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. 191 Jun 85

A novel endogenous inhibitor of the proteasome (high molecular weight multicatalytic protease) has been isolated and characterized from human erythrocytes. After purification by ion-exchange and sizing chromatography, the inhibitor displayed a native molecular mass of approximately 200 kDa and contained a single subunit of 50 kDa with an isoelectric point of 6.9. Although the inhibitor noncompetitively blocks proteolysis of [methyl-14C]-alpha-casein (Ki = 7.1 x 10(-8) M) and inhibits hydrolysis of Suc-Leu-Leu-Val-Tyr-AMC, it did not affect hydrolysis of other peptide substrates, such as MeOSuc-Phe-Leu-Phe-MNA and Z-Ala-Arg-Arg-MNA. To further characterize the 50-kDa inhibitor, a monoclonal antibody (MI-8) was generated that showed specific binding upon Western blot analysis of both native PAGE and SDS-PAGE. Immunoprecipitation with MI-8 specifically removed inhibitor activity against the proteasome. The 50-kDa inhibitor is distinct from a previously described 40-kDa inhibitor of the proteasome (Murakami, K., & Etlinger, J.D. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7588-7592) on the basis of lack of cross-reactivity with MI-8 and dissimilar peptide digest patterns. It is suggested that these endogenous inhibitors may have a role in ATP/ubiquitin-dependent proteolysis and/or other cellular functions involving this protease.
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PMID:Isolation and characterization of a novel endogenous inhibitor of the proteasome. 191 59

Four protein isoforms of the human CD46 molecule (MCP) have been identified using rabbit antisera against synthetic peptides corresponding to predicted cytoplasmic carboxyl-terminal sequences. Two different cytoplasmic tails, CD46 CYT 1 and CD46 CYT 2, were detected in CD46 molecules isolated from almost every cell type examined. Bands of 56 and 66 kDa were obtained from SDS-PAGE analyses of various cell types with both CYT 1 and CYT 2 antisera, which indicated that the size polymorphism of the CD46 molecule is not due to variations in the cytoplasmic tail and that each species contained two different sized molecules.
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PMID:Identification of four different CD46 (MCP) molecules with anti-peptide antibodies. 195 14

1. Proteasomes (multicatalytic proteinases) have been purified from spermatozoa and eggs of sea urchins by successive chromatographies on DEAE-cellulose, hydroxylapatite, and Sepharose 6B. 2. The isolated sperm and egg proteasomes showed similar properties such as molecular weight (both 630,000) and multiple catalytic activity (pH optimum, substrate specificity, inhibitor-susceptibility and SDS-stimulation). 3. Distinct protein components were detected between sperm and egg proteasomes by SDS-polyacrylamide gel electrophoresis and immunoblot analysis using antibody against egg proteasome.
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PMID:Comparative studies on proteasomes (multicatalytic proteinases) isolated from spermatozoa and eggs of sea urchins. 195 31

1. A high-molecular-mass multicatalytic proteinase, ingensin, has been purified from rat liver and biochemically characterized. Trypsinization in the presence of ATP prevented the degradation of ingensin subunits. 2. Glutaraldehyde, which copolymerizes proteins, increased the apparent molecular mass of the subunits on SDS-PAGE, indicating the occurrence of covalent crosslinking of subunits. ATP, in this case, lowered the extent of covalent crosslinking. These results suggest that ATP altered the conformation of ingensin subunits. 3. Urea-induced autodigestion experiments demonstrated that some low-molecular-weight subunits selectively disappeared without changes in the contents of other subunits. The chymotryptic activity of the proteinase was more resistant to autodigestion than its tryptic activity. Therefore, we conclude that separate subunits of the enzyme are responsible for the different peptide-hydrolyzing activities.
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PMID:Molecular and biochemical properties of the ATP-stimulated multicatalytic proteinase, ingensin, from rat liver. 212 26

Chicken liver multicatalytic proteinase is composed of multiple components with molecular masses ranging from 23 to 34 kDa and has 'chymotrypsin-like' and 'trypsin-like' activities, which were examined by using the chromogenic peptide substrates, succinyl-Phe-Leu-Phe-pNA(p-nitroanilide) and N-benzoyl-Phe-Val-Arg-pNA, respectively. Treatment of the enzyme with diisopropyl fluorophosphate (DFP) completely abolished the 'chymotrypsin-like' activity, but had little effect on the 'trypsin-like' activity. In the experiment with radio-labeled DFP, SDS-PAGE of the modified enzyme revealed that the radioactivity was incorporated into only the smallest subunit (23 kDa). The migration of this subunit was retarded on SDS-PAGE after the treatment with DFP.
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PMID:'Chymotrypsin-like' activity of chicken liver multicatalytic proteinase resides in the smallest subunit. 226 74


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