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)

A multicatalytic proteinase from rat skeletal muscle contains active site(s) catalysing the degradation of benzoyl-Val-Gly-Arg 4-methyl-7-coumarylamide, succinyl-Ala-Ala-Phe 4-methylcoumarylamide and [14C]methylcasein as well as benzyloxy-carbonyl-Leu-Leu-Glu 2-naphthylamide. These activities are 7-14-fold activated by 1 mM-sodium dodecyl sulphate. The activation leads to a higher susceptibility to the proteinase inhibitor chymostatin and to a lower ability to be inhibited and precipitated by antibodies raised against the non-activated enzyme. Since no changes in Mr or subunit composition were observed in the SDS-activated form, some conformational changes seem to occur during the activation step. More pronounced activation was observed in the presence of physiological concentrations of fatty acids; oleic acid at 100 microM concentrations stimulated the proteinase about 50-fold. In contrast with the non-activated proteinase, the activated enzyme considerably degrades muscle cytoplasmic proteins in vitro. Thus it is not unlikely that, in vivo, potential activators such as fatty acids can induce the multicatalytic proteinase to participate in muscle protein breakdown.
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PMID:Activation of the multicatalytic proteinase from rat skeletal muscle by fatty acids or sodium dodecyl sulphate. 389 Aug 40

Pure milk-clotting protease (MCP-76) is isolated by isotachophoresis at pH 5.0. The native molecule has only one protein chain. It is a metaloenzyme containing zinc. The pure MCP-76 has a molecular weight of 33 000 (+/- 1500) and by diphenyl-indenonyl-isothiocyanate method showed arginine as N-terminal amino acid.
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PMID:Preparation and some chemical characteristics of milk-clotting protease from Bacillus mesentericus 76. 701 83

The inhibitor protein I kappa B alpha controls the nuclear import of the transcription factor NF-kappa B. The inhibitory activity of I kappa B alpha is regulated from the cytoplasmic compartment by signal-induced proteolysis. Previous studies have shown that signal-dependent phosphorylation of serine residues 32 and 36 targets I kappa B alpha to the ubiquitin-proteasome pathway. Here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of I kappa B alpha. Conservative Lys-->Arg substitutions at both Lys-21 and Lys-22 produce dominant-negative mutants of I kappa B alpha in vivo. These constitutive inhibitors are appropriately phosphorylated but fail to release NF-kappa B in response to multiple inducers, including viral proteins, cytokines, and agents that mimic antigenic stimulation through the T-cell receptor. Moreover, these Lys-->Arg mutations prevent signal-dependent degradation of I kappa B alpha in vivo and ubiquitin conjugation in vitro. We conclude that site-specific ubiquitination of phosphorylated I kappa B alpha at Lys-21 and/or Lys-22 is an obligatory step in the activation of NF-kappa B.
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PMID:Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. 747 76

Pen a 1, the major shrimp allergen from the brown shrimp Penaeus aztecus was purified by preparative SDS-PAGE. Peptides were generated from Pen a 1 by CNBr cleavage and endoproteinase (Lys-C, Glu-C, trypsin, alkaline protease, Arg-C, chymotrypsin) digestion. The molecular weights of the resulting CNBr cleavage and enzymatic digestion products, separated by peptide SDS-PAGE, ranged from 1.5 to 20 kD. Following SDS-PAGE and semidry blotting, the analysis of monoclonal antibody (mAb) and subjects' IgE reactivities demonstrated that with the exception of alkaline protease, all cleavage procedures yielded IgE-binding peptides. However, since not all peptides of every digest bind IgE, it appears that IgE-binding epitopes are restricted to certain parts of the Pen a 1 molecule. mAbs bound to CNBr, Lys-C, trypsin, Glu-C and Arg-C peptides. Since mAbs reacted to several peptides from the same digest, Pen a 1 may have several similar epitopes. The comparison of IgE and mAb reactivities demonstrated similar but not identical binding patterns.
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PMID:Antigenic analysis (IgE and monoclonal antibodies) of the major shrimp allergen Pen a 1 (Tropomyosin) from Penaeus aztecus. 754 76

The ability of minigene-encoded viral peptide epitopes to be presented by class I molecules in the absence of MHC-encoded transporters has been evaluated in mutant T2 cells. These cells have a large deletion in the class II MHC region that includes the known transporter protein for antigenic peptides and proteasome genes and they are defective in presenting viral epitopes to CTL. T2 cells that express minigenes encoding the influenza virus matrix peptide 58-66 (GILGFVFTL) and two HTLV 1 Tax peptides 11-19 (LLFGYPVYV) and 12-19 were lysed by HLA-A2-restricted peptide-specific CTL. Minigene expression of a HLA-A2-restricted HIV reverse transcriptase peptide 476-484 (ILKEPVHGV) with three charged residues sensitized T2 cells poorly for lysis by HIV-specific CTL unless the peptide was preceded by an endoplasmic reticulum translocation signal sequence. Expression of an influenza virus nucleoprotein peptide 383-391 (SRYWAIRTR) with three charged arginine residues did sensitize HLA-B27+ T2 cells for lysis by peptide-specific CTL. These and other results with endogenously expressed peptide analogs in which hydrophobic and charged amino acids were interchanged demonstrate that antigenic peptides can be translocated from the cytoplasm into the class I Ag presentation pathway independent of MHC-encoded transporters; and that peptide hydrophobicity appears not to be a major determinant in selecting peptides for this alternate pathway.
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PMID:Presentation of endogenous peptides to MHC class I-restricted cytotoxic T lymphocytes in transport deletion mutant T2 cells. 767 94

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In eukaryotes, the N-end rule pathway is a ubiquitin-dependent, proteasome-based system that targets and processively degrades proteins bearing certain N-terminal residues. Arg-DHFR, a modified dihydrofolate reductase bearing an N-terminal arginine (destabilizing residue in the N-end rule), is short lived in ATP-supplemented reticulocyte extract. It is shown here that methotrexate, which is a folic acid analog and high affinity ligand of DHFR, inhibits the degradation but not ubiquitination of Arg-DHFR by the N-end rule pathway. The degradation of other N-end rule substrates is not affected by methotrexate. We discuss implications of these results for the mechanism of proteasome-mediated protein degradation.
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PMID:Methotrexate inhibits proteolysis of dihydrofolate reductase by the N-end rule pathway. 771 22

The ACE inhibitory activity of an alkaline protease hydrolyzate from sardine muscle did not change after being treated by gastrointestinal proteases (IC50 = 0.082 mg protein/ml). Eleven new ACE inhibitory peptides, constructed with 2 to 4 amino acid residues, were isolated from the hydrolyzate. The ACE inhibitory activity of each was mostly below 100 microM of IC50 value; the maximal inhibitory activity was observed for Lys-Trp (IC50 = 1.63 microM). The isolated peptides inhibited ACE competitively, except for Met-Tyr with non-competitive inhibition. As the result of sequence homology, Arg-Val-Tyr isolated from the hydrolyzate was found in the primary structure of angiotensins I, II, and III, and of des As[1]-angiotensin I.
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PMID:Angiotensin I-converting enzyme inhibitory peptides in an alkaline protease hydrolyzate derived from sardine muscle. 776 18

Although human leukocyte antigen (HLA) B27 has been directly implicated in the pathogenesis of ankylosing spondylitis (AS), additional evidence favours the involvement of an additional genetic factor(s). In a previous population analysis of AS patients selected for a history of acute anterior uveitis (AAU), we had demonstrated a phenotypic association between polymorphism in an HLA-linked proteasome subunit gene, LMP2, and the development of AAU and peripheral arthritis. In the present study, we have assessed the relative risk of homozygosity for the LMP2 arginine variant, the disease-associated genotype, for these complications in an unselected group of 86 patients with AS seen sequentially in 1 centre by 1 rheumatologist over a 2-y period. LMP2 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using the CfoI restriction enzyme. Homozygosity for the LMP2 arginine variants was observed in 68.4% of AS patients who had had AAU as compared to 41.7% without AAU (relative risk 3.0; chi 2 = 6.1, p < 0.02). The proportion of AS patients with peripheral arthritis homozygous for the arginine residue was 55.2% as compared to 52.6% without this complication (relative risk 1.1; p > 0.05). Our data suggest a primary association with the development of AAU and provide evidence for genetic heterogeneity in distinct clinical subgroups of patients with AS as a basis for phenotypic variation.
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PMID:Polymorphism in the LMP2 gene influences the relative risk for acute anterior uveitis in unselected patients with ankylosing spondylitis. 776 65

Rational shift of the optimum pH toward alkalinity and enhancement of thermostability were investigated by using a thermostable extremely alkaline protease (optimum pH, 12 to 13) from the alkaliphilic and thermophilic Bacillus sp. strain B18'. The protease gene (aprM) was cloned, and the sequence analysis revealed an open reading frame of 361 amino acids that was composed of a putative signal sequence (24 amino acids), a prosequence (69 amino acids), and a mature enzyme (268 amino acids) (molecular weight, 27,664). The amino acid sequence of this protease was compared with those of other serine proteases. A direct correlation of higher optimum pH with an increase in the number of arginine residues was observed. An even more thermostable mutant enzyme was created by introducing a point mutation. When the position of the beta-turn, Thr-203, was replaced by Pro, the residual activity of this mutant enzyme at 80 degrees C for 30 min was higher than that of the wild-type enzyme (50% versus 10%). The specific activity of this mutant enzyme at 70 degrees C was 105% of that of the wild-type enzyme under nondenaturation condition. These data suggest that the higher content of Arg residues favors the alkalinity of the serine protease and that introduction of a Pro residue into the beta-turn structure stabilizes the enzyme.
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PMID:Stabilization and rational design of serine protease AprM under highly alkaline and high-temperature conditions. 798 36

An allele of mutation in the proteasome subunit gene Y7, y7-1, caused a temperature-sensitive growth in S. cerevisiae. One of the multi-copy suppressor genes for this growth defect was identical to SSB1, which encodes a 70-kDa heat shock cognate protein of the yeast. Introduction of the multi-copy SSB1 gene into the y7-1 mutant cells suppressed defects in the degradation of X-beta-galactosidase (X = Arg or Pro) observed in the mutant cells. Thus, the SSB1 protein, one of the chaperons of the yeast, facilitated intracellular protein degradation.
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PMID:A 70-kDa heat shock cognate protein suppresses the defects caused by a proteasome mutation in Saccharomyces cerevisiae. 808 77


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