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:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating M antigen, specific for genus Schistosoma, was previously described in serum, urine, patients' milk, and in serum and urine of animals infected by S. mansoni. The M antigen was thermostable and soluble in trichloroacetic acid. It was not hydrolyzed by protease, ribonuclease, amylase, or neuraminidase but destroyed by sodium metaperiodate. In the present study, we have purified the M ag by using trichloroacetic acid solubility, DEAE Sephadex, and immunoadsorption. The M ag showed a neutral electric charge, a m.w. heterogeneity, and was only stained by periodic acid-Schiff. The composition study revealed M ag was a glycoprotein with a polysaccharide moiety (63% of the molecules) particularly rich in galactose, fucose, glucosamine, and mannose, and with a high molecular ratio of serine and threonine. The presence of O-glycosidic linkage allowed M ag to be considered as a mucin or a mucus glycoprotein-like component. It was localized in the cell wall of the gut of adult worms.
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PMID:Purification, immunochemical, and biologic characterization of the Schistosoma circulating M antigen. 698 17

A procedure for the preparation of porcine protease E is described. The availability of a convenient source of the enzyme has permitted specificity studies utilizing the macromolecular substrates oxidized insulin A and B chains and oxidized ribonuclease. The results show that protease E has a pronounced selectivity for the carbonyl bonds of serine threonine, alanine, and valine residues, with the latter most favored. The specificity is complementary to that of the chymotrypsins and we suggest that this property is physiologically significant. The k3 and Km values for the substrates acetyl-trialanine methyl ester, succinyltrialanine p-nitroanilide and benzoylalanine methyl ester are comparable to those observed by others for porcine elastase. The specificity observed in the present work, however, indicates that protease E may best be regarded as a member of the chymotrypsin group of enzymes.
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PMID:The specificity of porcine pancreatic protease E. 700 83

We have been searching for enzyme inhibitors in culture filtrates of microbes and have found leupeptin, antipain, chymostatin, elastatinal, pepstatin, hydroxypepstatin, pepstanone and phosphoramidon as specific inhibitors of serine, thiol, carboxyl and metallo proteases. We found significant activities of aminopeptidases, phosphatase and esterase on surface membranes of various mammalian cells. We discovered bestatin, amastatin, forphenicine, esterastin and ebelactones A and B as specific inhibitors against these enzymes. These inhibitors were proved to bind to cells and modify immune responses. The usefulness of bestatin in cancer treatment has been suggested by clinical studies. It has been shown by several investigators that some endopeptidases such as Ca2+-activated neutral proteases and some other serine proteases may play important roles in muscular dystrophy. In addition to these endopeptidases, we found an abnormal increase in various enzyme activities in dystrophic mice and chickens. Especially, aminopeptidase activities are markedly increased. Moreover, its inhibitor bestatin became interesting on the aspects of its binding to cell surfaces. Bestatin and leupeptin which inhibit Ca2+-dependent protease showed some therapeutic effects against mouse dystrophy. Investigating enzyme activities in synovial fluid of patients with rheumatoid arthritis and osteoarthritis, we found increased activities of aminopeptidases, chymotrypsin-like enzyme, and phosphatase in rheumatoid arthritis but not in osteoarthritis. In chronic hemodialysis patients, RNase activity in serum is markedly elevated. Thus, enzyme inhibitors are increasing their potential usefulness in treatment of various diseases.
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PMID:The relationships between enzyme inhibitors and function of mammalian cells. 704 7

Phosphoenolpyruvate carboxykinase (PEPCK) is the rate-limiting enzyme of gluconeogenesis. This metabolically important enzyme is unique in that it has no known allosteric modifiers, and all of the regulation of its activity is exerted at the level of gene expression. The expression of the PEPCK gene in liver is elevated in most forms of diabetes, and plays a major contributory role in the hyperglycemia characteristic of this disease. In this study, we initiated studies to determine the molecular basis for the increased PEPCK gene expression in diabetes. RNase protection assays of RNA isolated from control, streptozotocin-induced diabetic, and insulin-treated diabetic rat liver indicated that PEPCK mRNA levels are elevated two- to threefold in diabetic rat liver compared to controls. Nuclear run-on assays indicated that the increased PEPCK mRNA levels can be fully accounted for by changes in the transcription rate of the gene. We next initiated characterization of the cAMP response element binding protein (CREB) in diabetic rat liver, since it is known to play a major role in mediating the it is known to play a major role in mediating the basal transcriptional activity of the PEPCK gene as well as the cAMP-dependent stimulation of PEPCK gene transcription, the latter through the phosphorylation of serine 133 of CREB. Western blot analysis of nuclear lysates prepared from rat livers indicated that CREB protein levels in diabetic rat liver nuclei were similar to those of controls. However, using an antibody which specifically recognizes the serine 133-phosphorylated form of CREB, we found that the levels of phospho-CREB were significantly decreased in diabetic rat liver, an effect which insulin treatment reversed. This observation suggests that overexpression of the PEPCK gene in diabetes is not linked to the cAMP signaling system in liver.
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PMID:The phosphorylation state of the cAMP response element binding protein is decreased in diabetic rat liver. 748 14

Transforming growth factor-beta 1 (TGF-beta 1) induces angiogenesis in vivo and capillary morphogenesis in vitro. Two receptor serine/threonine kinases (types I and II) have been identified as signal transducing TGF-beta receptors. We explored the possibility of inhibiting TGF-beta-mediated events in glomerular capillary endothelial cells using a TGF-beta type II receptor (T beta R-II) transdominant negative mutant. A mutant TGF-beta type II receptor (T beta R-IIM), lacking the cytoplasmic serine/threonine kinase domain, was produced by polymerase chain reaction using rat T beta R-II cDNA as template. Since T beta R-II and TGF-beta type I receptor (T beta R-I) heterodimerize for signal transduction, the mutant receptor competes for binding to wild-type T beta R-I, hence acting in a dominant negative fashion. Glomerular capillary endothelial cells were stably transfected with T beta R-IIM, and four independent clones were expanded. That the T beta R-IIM mRNA was expressed was shown by reverse transcriptase-polymerase chain reaction, RNase protection assay, and Northern analysis. Presence of cell surface T beta R-IIM protein was shown by affinity cross-linking with 125I-TGF-beta 1. In wild-type endothelial cells, TGF-beta 1 (2 ng/ml) significantly inhibited [3H]thymidine incorporation to 63 +/- 10% of control (n = 4). In transfected endothelial cells carrying T beta R-IIM, TGF-beta 1 stimulated [3H]thymidine incorporation to 131 +/- 9% of control (n = 4, p < 0.005). Also, in wild-type endothelial cells, endogenous and exogenous TGF-beta 1 induced apoptosis and associated capillary formation. Both apoptosis and capillary formation were uniformly and entirely absent in transfected endothelial cells carrying T beta R-IIM. This represents the first demonstration that capillary morphogenesis in vitro is associated with apoptosis, and that interference with T beta R-II signaling inhibits this process in glomerular capillary endothelial cells.
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PMID:Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors. 767 46

Because mutations in receptor tyrosine kinases may contribute to cellular transformation, studies were undertaken to examine c-kit in human leukemia. Isoforms of c-kit have been characterized in the human megakaryoblastic leukemia cell line M-07. Deletion of the four amino acids Gly-Asn-Asn-Lys in the extracellular domain represents an alternatively spliced isoform that has been shown by others, in mice, to be associated with constitutive receptor autophosphorylation (Reith et al, EMBO J 10:2451, 1991). Additional isoforms differ in the inclusion or exclusion of a serine residue in the interkinase domain, a region that contains the binding site for phosphatidylinositol 3-kinase. By RNase protection analysis, we have shown coexpression of the Gly-Asn-Asn-Lys+ and Gly-Asn-Asn-Lys- isoforms, with dominance of the Gly-Asn-Asn-Lys- transcript, in normal human bone marrow, normal melanocytes, a range of tumor cell lines, and the blasts of 23 patients with acute myeloid leukemia. Analysis of transcripts for the Ser+ and Ser- isoforms also showed coexpression in all normal and leukemic cells examined. The ratios of isoform expression for both the Gly-Asn-Asn-Lys and Ser variants were relatively constant, providing no evidence in the tumors examined that upregulation of one isoform contributes to the neoplastic process.
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PMID:Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. 768 88

The relationship between the clinical severity of osteogenesis imperfecta (OI) and the location and type of amino acid substitution in type I collagen is not identical for mutations in the alpha 1(I) and alpha 2(I) chains. Furthermore, the alpha 2(I) chain, once thought to be associated with moderate forms of OI, has now been associated with approximately as many lethal as non-lethal cases. We describe two novel substitutions for glycine in the alpha 2(I) chain, one associated with a lethal phenotype in twins and the other with a moderate non-lethal phenotype. The type I collagen of all probands was characterized electrophoretically by two populations of alpha chains, one normal and one with delayed migration. Cyanogen bromide peptides of the overmodified alpha 1(I) chains revealed delayed migration of all peptides except CB6. The indicated target region of alpha 1(I) and alpha 2(I) cDNA of the probands was analyzed by RNA-DNA hybrid analysis with RNase A digestion. All probands had mismatches in the region of alpha 2(I) coding for amino acids 642-912. The lethal phenotype was associated with a G-->A mutation, resulting in Gly706-->serine; the non-lethal mutation was a G-->T change resulting in Gly676-->valine. Both mutations occurred de novo in the probands; parental leukocyte DNA was normal. In conjunction with the previously described exon deletions and point mutations in alpha 2(I), these mutations define five alternating non-lethal/lethal regions along the chain and support a regional, as opposed to a gradient, model of OI pathophysiology. These mutations in particular help to define a lethal/non-lethal junction at about alpha 2(I) amino acid 700.
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PMID:Two additional cases of osteogenesis imperfecta with substitutions for glycine in the alpha 2(I) collagen chain. A regional model relating mutation location with phenotype. 769 12

Glutaredoxin (Grx) contains a redox-active disulfide and catalyzes thiol-disulfide interchange reactions with specificity for GSH. The dithiol form of Grx reduces mixed disulfides involving GSH or protein disulfides. During oxidative refolding of 8 microM reduced and denatured ribonuclease RNase-(SH)8 in a redox buffer of 1 mM GSH and 0.2 mM GSSG to yield native RNase-(S2)4, a large number of GSH-mixed disulfide species are formed. A lag phase that precedes formation of folded active RNase at a steady-state rate was shortened or eliminated by the presence of a catalytic concentration (0.5 microM) of Escherichia coli Grx together with protein disulfide-isomerase (PDI), its procaryotic equivalent E. coli DsbA, or the PDI analogue the E. coli thioredoxin mutant protein P34H. A mutant Grx in which one of the active site cysteine residues (Cys-11 and Cys-14) had been replaced by serine, C14S Grx, had similar effect compared with its wild-type counterpart. This demonstrated that Grx acted by a monothiol mechanism involving only Cys-11 and that RNase-S-SG-mixed disulfides were the substrates. Grx displayed synergistic activity together with PDI only in GSH/GSSG redox buffers with sufficiently low redox potential (E'0 of -208 or -181 mV) to allow reduction of the active site of Grx. In refolding systems that do not depend on glutathione, like cystamine/cysteamine or in the presence of selenite (SeO3(2-)), no synergistic activity of Grx was observed with PDI. We conclude that Grx acts by reducing mixed disulfides between GSH and RNase that are rate-limiting in enzyme-catalyzed refolding.
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PMID:Glutaredoxin accelerates glutathione-dependent folding of reduced ribonuclease A together with protein disulfide-isomerase. 771 72

Bovine seminal ribonuclease (BS-RNase) is a homolog of RNase A with special biological properties that include specific antitumor, aspermatogenic, and immuno-suppressive activities. Unlike RNase A, BS-RNase is a dimer cross-linked by disulfide bonds between Cys31 of one subunit and Cys32 of the other. At equilibrium, this dimer is a mixture of two distinct quaternary forms, M = M and M x M. The conversion of M = M to M x M entails the exchange of NH2-terminal alpha-helices between subunits. Here, the cytotoxic activities of purified M x M were shown to be greater than those of purified M = M, despite extensive equilibration of M = M and M x M during the time course of the assays. Replacing Cys31 or Cys32 with a serine residue did not compromise the enzymatic activity of dimeric BS-RNase, but reduced both the fraction of M x M at equilibrium and the cytotoxicity. We conclude that the M x M form is responsible for the special biological properties of BS-RNase. Since cytosolic ribonuclease inhibitor binds tightly to monomeric but not dimeric BS-RNase and only the M x M form can remain dimeric in the reducing environment of the cytosol, we propose that BS-RNase has evolved its M x M form to retain its lethal enzymatic activity in vivo.
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PMID:Structural basis for the biological activities of bovine seminal ribonuclease. 773 87

Nuclear respiratory factor 2 (NRF-2) was previously purified to near homogeneity from HeLa cells on the basis of its ability to bind tandem recognition sites in the rat cytochrome oxidase subunit IV (RCO4) promoter. It consisted of five subunits, alpha, beta 1, beta 2, gamma 1, and gamma 2. Sequencing of tryptic peptides from alpha and from mixtures of the two beta or two gamma subunits revealed sequence identities with subunits of the mouse GA-binding protein (GABP), a ubiquitously expressed ETS domain activator composed of three subunits, alpha, beta 1, and beta 2. To understand the precise relationship between NRF-2 and GABP, cDNAs for all five NRF-2 subunits have now been cloned and their products have been overexpressed. The results establish that the two additional NRF-2 subunits are molecular variants that differ from GABP beta 1 and beta 2 by having a 12-amino-acid insertion containing two serine doublets. PCR and RNase protection assays show that mRNAs for these variants are expressed in the human but not the rodent cells and tissues examined. The insertion did not alter the ability of the beta and gamma subunits to associate with alpha, the DNA-binding subunit, nor did it affect the ability of NRF-2 beta 1 or beta 2 to direct high-affinity binding of alpha to tandem sites in the RCO4 promoter. In addition, the four NRF-2 beta and gamma subunits were equally proficient in activating transcription in transfected cells when fused to a GAL4 DNA-binding domain. The domain responsible for this transcriptional activation was localized by deletion mapping to a region of approximately 70 amino acids that is conserved in all four NRF-2 beta and gamma subunits. The repeated glutamine-containing hydrophobic clusters within this region bear a strong resemblance to those recently implicated in protein-protein interactions within the transcriptional apparatus.
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PMID:Four structurally distinct, non-DNA-binding subunits of human nuclear respiratory factor 2 share a conserved transcriptional activation domain. 779 16


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