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 cold-adapted protease MCP-01 was obtained from deep-sea psychrotrophic bacterium Pseudoaltermonas sp. SM9913. The effects of four different buffers, all at 50 mmol/l concentration, on its thermostability and autolysis were studied. The autolysis process of MCP-01 was studied by capillary electrophoresis. The thermostability of MCP-01 increased successively in the following order: carbonate < Tris < phosphate < borate. The optimum temperature for casein hydrolysis also increased in the same order. This suggested that the conformation of MCP-01 was flexible and its autolytic susceptibility was affected by some factors in the buffers such as charge and ionic species. The results also showed that different buffers, in addition to affecting the autolysis speed, gave different patterns of autolysis products. In carbonate buffer, Tris buffer, phosphate buffer and borate buffer, the autolysis patterns of MCP-01 were different. These results suggested that protease MCP-01 probably have different conformations in different buffers, thus exposing different autolysis sites on the enzyme surface. In addition, the loss of activity correlated with the speed of autolysis in the four different buffers, showing that autolysis may be a reason for the low thermostability of the enzyme.
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PMID:Effects of different buffers on the thermostability and autolysis of a cold-adapted protease MCP-01. 1263 54

Monocrotophos (dimethyl (E)-1-methyl-2-(methylcarbamoyl) vinyl phosphate, or MCP), an organophosphorus insecticide, was used as a sole phosphorus source by the microorganisms isolated from the soil. None of the isolates could utilize MCP as a sole source of carbon. Two of the potential microbial isolates, Pseudomonas aeruginosa F10B and Clavibacter michiganense subsp. insidiosum SBL 11, could utilize MCP as a sole source of phosphorus. Pseudomonas aeruginosa F10B showed a lag phase of 4 h, while in the case of C. michiganense subsp. insidiosum SBL 11, it was 8 h when cultured in the presence of MCP. The generation time for both strains was increased in the medium containing MCP. It was 2.15 h for P. aeruginosa F10B in MCP medium as compared with 1.29 h in basal medium, while in case of C. michiganense subsp. insidiosum SBL 11 it was increased to 3.4 h in MCP medium as compared with 1.28 h in basal medium. These two strains were able to degrade technical MCP in shake-flask culture up to 98.9 and 86.9%, respectively, and pure MCP up to 79 and 80%, respectively, within 24 h at 37 degrees C. The optimal concentration of MCP required for the normal growth was 500 ppm. In the substrate preference study, Tris-p-nitrophenyl phosphate was the most preferred substrate followed by paraoxon. The enzyme responsible for the break down of MCP was phosphotriesterase, which was localized on the membrane-bound fraction of the disrupted cells. The gene responsible for the production of phosphotriesterase (opd) in P. aeruginosa F10B was plasmid-borne.
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PMID:Utilization of monocrotophos as phosphorus source by Pseudomonas aeruginosa F10B and Clavibacter michiganense subsp. insidiosum SBL 11. 1271 98

Cadmium (Cd(2+)) is a non-essential heavy metal, which is taken up from the environment into the body through pulmonary and enteral pathways. The S1 segment of the kidney proximal tubule (PT) is a major target of chronic Cd(2+) toxicity. Renal dysfunction develops in up to 7% of the general population and in its most severe form displays major features of Fanconi syndrome, such as a defective protein, amino acid, glucose, bicarbonate and phosphate reabsorption. The major pathway for Cd(2+) uptake by PT cells (PTCs) in vivo is apical endocytosis of Cd(2+) complexed to the high-affinity metal-binding protein metallothionein (MT), which may be receptor-mediated. MT is subsequently degraded in endo-lysosomes, and Cd(2+) is liberated for translocation into the cytosolic compartment, possibly using transporters for Fe(2+), Zn(2+) or Cu(2+), such as the divalent metal transporter DMT1. Free Cd(2+) ions in the extracellular space are translocated across apical and/or basolateral PTC membranes into the cytosol via transporters, whose identity remains unknown. Cytosolic Cd(2+) generates reactive oxygen species (ROS), which deplete endogenous radical scavengers. ROS also damage a variety of transport proteins, including the Na(+)/K(+)-ATPase, which are subsequently degraded by the proteasome and endo-lysosomal proteases. Cd(2+) causes mitochondrial swelling and release of cytochrome C. If these ROS-mediated stress events are not balanced by repair processes, affected cells undergo apoptosis. But Cd(2+) also induces the upregulation of cytoprotective stress and metal-scavenging proteins, such as MT. In addition, Cd(2+) upregulates the detoxifying pump multidrug resistance P-glycoprotein, which appears to protect PTCs against Cd(2+)-induced apoptosis. Thus, Cd(2+) interferes with various cellular events ranging from mechanisms of induction of programmed cell death to activation of cell survival genes. A better understanding of the cellular mechanisms involved in Cd(2+) nephrotoxicity should provide insights into other heavy metal (e.g. Pb(2+), Hg(2+)) nephropathies and various forms of acquired Fanconi syndrome.
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PMID:Nephrotoxicity and the proximal tubule. Insights from cadmium. 1275 69

We screened the putative rap-phr (response regulator aspartyl-phosphate phosphatase-phosphatase regulator) systems identified in the Bacillus subtilis genome for a rap gene that affects aprE (alkaline protease gene) expression by using a multicopy plasmid. We found that rapG was involved in the regulation of aprE, which belongs to the regulon of DegU, the response regulator of the DegS-DegU two-component system. Disruption of rapG and phrG resulted in enhancement and reduction of aprE-lacZ expression, respectively, suggesting that PhrG inhibits RapG activity. Addition of 1-30 nM of a synthetic pentapeptide (PhrG; NH2-EKMIG-COOH) to the phrG disruptant completely rescued aprE-lacZ expression, indicating that the PhrG peptide is indeed involved in aprE-lacZ expression. Surprisingly, either introduction of multicopy phrG or addition of the PhrG peptide at high concentrations (100-300 nM) to the phrG cells decreased aprE-lacZ expression. These results are reminiscent of the previous observation that at higher concentrations the PhrC peptide inhibits srfA-lacZ expression directed by ComA, the regulator of the ComP-ComA two-component system. Because the Rap proteins belong to a family of aspartyl protein phosphatases, we tried to investigate the possible influence of RapG on dephosphorylation of DegU-P (phosphorylated DegU) in vitro. RapG, however, did not affect dephosphorylation of DegU-P under the adopted experimental conditions. Therefore, we hypothesized that RapG might inhibit the binding activity of DegU to the target promoters. We analysed the interaction of DegU and RapG using the aprE promoter and another target, a comK promoter. Gel shift analysis revealed that RapG served as the inhibitor of DegU binding to the promoter regions of aprE and comK and that this inhibition was counteracted by the PhrG peptide.
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PMID:Binding of response regulator DegU to the aprE promoter is inhibited by RapG, which is counteracted by extracellular PhrG in Bacillus subtilis. 1295 Sep 30

A protein-protein association regulated by phosphorylation of serine is examined by NMR studies. Degradation of the HIV receptor CD4 by the proteasome, mediated by the HIV-1 protein Vpu, is crucial for the release of fully infectious virions. Phosphorylation of Vpu at two sites, Ser52 and Ser56, on the motif DSGXXS is required for the interaction of Vpu with the ubiquitin ligase SCF-betaTrCP which triggers CD4 degradation by the proteasome. This motif is conserved in several signaling proteins known to be degraded by the proteasome. To elucidate the basis of beta-TrCP recognition, the bound conformation of the P-Vpu(41-62) peptide was determined by using NMR and MD. The TRNOE intensities provided distance constraints which were used in simulated annealing. The beta-TrCP-bound structure of P-Vpu was found to be similar to the structure of the free peptide in solution and to the structure recognized by its antibody. Residues 50-57 formed a bend while the phosphate groups are pointing away. The binding fragment was studied by STD-NMR spectroscopy. The phosphorylated motif DpS(52)GNEpS(56) was found to make intimate contact with beta-TrCP, and pSer52 displays the strongest binding effect. It is suggested that Ser phosphorylation allows protein-protein association by electrostatic stabilization: an obvious negative binding region of Vpu was recognizable by positive residues (Arg and Lys) of the WD domain of beta-TrCP. The Ile46 residue was also found essential for interaction with the beta-TrCP protein. Leu45 and Ile46 side chains lie in close proximity to a hydrophobic pocket of the WD domain.
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PMID:NMR studies of the phosphorylation motif of the HIV-1 protein Vpu bound to the F-box protein beta-TrCP. 1467 48

A unifying feature of many neurodegenerative disorders is the accumulation of polyubiquitinated protein inclusions in dystrophic neurons, e.g. containing alpha-synuclein, which is suggestive of an insufficient proteasomal activity. We demonstrate that alpha-synuclein and 20 S proteasome components co-localize in Lewy bodies and show that subunits from 20 S proteasome particles, in contrast to subunits of the 19 S regulatory complex, bind efficiently to aggregated filamentous but not monomeric alpha-synuclein. Proteasome binding to insoluble alpha-synuclein filaments and soluble alpha-synuclein oligomers results in marked inhibition of its chymotrypsin-like hydrolytic activity through a non-competitive mechanism that is mimicked by model amyloid-Abeta peptide aggregates. Endogenous ligands of aggregated alpha-synuclein like heat shock protein 70 and glyceraldehyde-6-phosphate dehydrogenase bind filaments and inhibit their anti-proteasomal activity. The inhibitory effect of amyloid aggregates may thus be amenable to modulation by endogenous chaperones and possibly accessible for therapeutic intervention.
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PMID:Proteasomal inhibition by alpha-synuclein filaments and oligomers. 1471 27

Possible target proteins of cytosolic thioredoxin in higher plants have been investigated in the cell lysate of dark-grown Arabidopsis thaliana whole tissues. We immobilized a mutant of cytosolic thioredoxin, in which an internal cysteine at the active site was substituted with serine, on CNBr activated resin, and used the resin for the thioredoxin-affinity chromatography. By using this resin, the target proteins for thioredoxin in the higher plant cytosol were efficiently acquired. The obtained proteins were separated by two-dimensional gel electrophoresis and analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Thus we have identified proteins of the anti-oxidative stress system proteins (ascorbate peroxidase, germin-like protein, and monomeric type II peroxiredoxin), proteins involved in protein biosynthesis (elongation factor-2 and eukaryotic translation initiation factor 4A), proteins involved in protein degradation (the regulatory subunit of 26S proteasome), and several metabolic enzymes (alcohol dehydrogenase, fructose 1,6-bis phosphate aldolase-like protein, cytosolic glyceraldehyde 3-phosphate dehydrogenase, cytosolic malate dehydrogenase, and vitamin B(12)-independent methionine synthase) together with some chloroplast proteins (chaperonin 60-alpha and 60-beta, heat shock protein 70, and glutamine synthase). The results in this study and recent proteomics studies on the target proteins of chloroplast thioredoxin indicate the versatility and the physiological significance of thioredoxin as reductant in plant cell.
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PMID:Target proteins of the cytosolic thioredoxins in Arabidopsis thaliana. 1474 82

Availability of phytate-bound P as influenced by supplemental phytase was studied in eight horses consuming four diets in a 4 x 4 Latin square design experiment. The treatments were a control (containing a low P level, 18.4 g/d) and three high-P diets. These diets contained P as monocalcium phosphate (MCP; 43.7 g/d), myoinositol hexakisphosphate in the form of wheat and rice bran (MIHP; 41.8 g/d), or MIHP with microbial phytase (MIHPP; 42.5 g/d). The proportions of phytate-bound P were 3, 1, 55, and 56% for the control, MCP, MIHP, and MIHPP, respectively. The MIHPP diet was supplemented with 300 phytase units (FTU)/kg (as-fed basis). Feces and urine were collected quantitatively and analyzed for P, Ca, and Mg. Urinary P excretion was lower (P < 0.05) with the control diet (0 g of P/d) than with the MCP diet (1.0 g of P/d). The low urinary P excretion (0.3 g of P/d) for the MIHP diet suggested low P availability compared with the MCP diet, but apparent digestibility of P expressed as a percentage of intake did not differ (P = 0.065) between these diets. Apparent Ca digestibility was lower (P < 0.05) for the MIHP diet than for the MCP diet (26.4 vs. 42.4%). This difference may have been caused by the origin of the Ca in these diets. Phytase supplementation increased apparent Ca digestibility from 26.4 to 31.5% (P < 0.05). Magnesium was not influenced by the level of phytate in the diet. Our data indicate that phytase supplementation had more influence on Ca digestibility than on P digestibility and suggest that phytase supplementation may be beneficial for improving Ca digestibility for horses receiving a phytate-rich diet.
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PMID:The apparent digestibility of phytate phosphorus and the influence of supplemental phytase in horses. 1521 3

Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr residues by the monosaccharide O-linked beta-N-acetylglucosamine (O-GlcNAc). The rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli, morphogens, the cell cycle and development suggests a key role for O-GlcNAc in signal transduction pathways. Modulation of O-GlcNAc levels has profound effects on the functioning of cells, in part mediated through a complex interplay between O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc modification and phosphorylation are reciprocal. That is, they occur on different subsets of the protein population, as the site of attachment occurs on the same or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the etiology of type II diabetes, the regulation of stress response pathways, and in the regulation of the proteasome.
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PMID:O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress. 1523 46

The eukaryotic 20S proteasome is the multifunctional catalytic core of the 26S proteasome, which plays a central role in intracellular protein degradation. Association of the 20S core with a regulatory subcomplex, termed PA700 (also known as the 19S cap), forms the 26S proteasome, which degrades ubiquitinated and nonubiquitinated proteins through an ATP-dependent process. Although proteolytic assistance by this regulatory particle is a general feature of proteasome-dependent turnover, the 20S proteasome itself can degrade some proteins directly, bypassing ubiquitination and PA700, as an alternative mechanism in vitro. The mechanism underlying this pathway is based on the ability of the 20S proteasome to recognize partially unfolded proteins. Here we show that the 20S proteasome recognizes the heat-denatured forms of model proteins such as citrate synthase, malate dehydrogenase. and glyceraldehydes-3-phosphate dehydrogenase, and prevents their aggregation in vitro. This process was not followed by the refolding of these denatured substrates into their native states, whereas PA700 or the 26S proteasome generally promotes their reactivation. These results indicate that the 20S proteasome might play a role in maintaining denatured and misfolded substrates in a soluble state, thereby facilitating their refolding or degradation.
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PMID:20S proteasome prevents aggregation of heat-denatured proteins without PA700 regulatory subcomplex like a molecular chaperone. 1524 66


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