Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zinc fingers 4 to 7 of Xenopus transcription factor IIIA (TFIIIA) represent the minimal polypeptide necessary for high-affinity binding to 5 S RNA. Mutations covering the entire 5 S RNA structure have been compared for their effects on the binding affinity of full-length TFIIIA and a polypeptide consisting of fingers 4 to 7 of TFIIIA (zf4-7). In addition, ribonuclease footprinting was used to compare the binding sites of TFIIIA and zf4-7 on 5 S RNA. The consistency between the data obtained from these two approaches provided a clear indication that zinc fingers 4 to 7 of TFIIIA bind to a central core region on the 5 S RNA molecule consisting of loop B/helix II/loop A/helix V/region E. This information was used to design a truncated 75-nucleotide-long RNA molecule that retains high affinity for zf4-7. Therefore, we conclude that the specific interaction of TFIIIA with 5 S RNA can be represented by a complex formed between a four zinc finger polypeptide and a truncated 5 S RNA molecule.
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PMID:Interaction of the RNA binding fingers of Xenopus transcription factor IIIA with specific regions of 5 S ribosomal RNA. 773 Oct 45

One of the three structural glycoproteins of classical swine fever virus (CSFV) is E0, a disulfide-bonded homodimer that induces virus-neutralizing antibodies and occurs in a virion-bound as well as a secreted form. E0 was shown to be similar to a family of fungal and plant ribonucleases. Purified E0 from CSFV-infected cells was a potent ribonuclease specific for uridine and inhibitable by zinc ions.
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PMID:Identification of a structural glycoprotein of an RNA virus as a ribonuclease. 835 50

Certain metal ions are known to be potent sensitizers, but the self proteins modified by metal ions and the self peptides recognized by 'metal-specific' T cells are unknown. In humans and mice treatment with gold anti-rheumatic drugs, containing Au(I), may lead to allergic and autoimmune side effects. Human and murine T cells do not react to Au(I), however, but to the reactive metabolite Au(III). Here we show that alteration by Au(III) of a model antigen, bovine ribonuclease (RNase)A, results in T cell sensitization to cryptic peptides of this protein. Upon immunization of mice with Au(III)-pretreated RNase [RNase/Au(III)], CD4+ T cell hybridomas specific for RNase/Au(III) were obtained in addition to those recognizing the immunodominant peptide RNase 74-88; the latter also were obtained after immunization with native RNase. RNase/Au(III)-specific T cell hybridomas reacted against RNase/Au(III) and RNase denatured by S-sulfonation of cysteine residues, but not against native RNase, or RNase pretreated with Au(I), A1(III), Cu(II), Fe(II), Fe(III), Ni(II), Mn(II), or Zn(II). Using a panel of overlapping, synthetic RNase peptides which were devoid of gold or gold-induced modifications, epitope mapping revealed that RNase/Au(III)-specific T cell hybridomas recognized the cryptic peptides 7-21 and 94-108, respectively. Comparison of the proliferative response of bulk CD4+ T cells, prepared from splenocytes after immunization with either RNase/Au(III) or native RNase, revealed that Au(III) pretreatment of RNase led to a markedly enhanced response to the two cryptic peptides while it did not influence the response to the immunodominant peptide. The cryptic peptides were also presented after preincubation of bone marrow-derived macrophages with RNase and Au(I), but not with RNase alone, suggesting that oxidation of Au(I) to Au(III) and subsequent protein alteration by Au(III) can happen in mononuclear phagocytes. We conclude that Au(III) alteration of proteins alters antigen processing and, thus leads to presentation of cryptic peptides. This mechanism may shed light on the development of allergic and autoimmune side effects of Au(I) anti-rheumatic drugs. In addition, it might provide a general mechanism of how metal ions act as T cell sensitizers.
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PMID:Alteration of a model antigen by Au(III) leads to T cell sensitization to cryptic peptides. 861 92

This paper describes the purification and properties of a 2',3'-cyclic nucleotide 3'-phosphodiesterase which hydrolyzes nucleoside 2',3'-cyclic monophosphates to nucleoside 2'-phosphates. The enzyme is present in encysted gastrulae of Artemia and its specific activity greatly increases during larval development. The purified enzyme has a molecular weight of around 55 000 as estimated by gel filtration, does not require metals for activity, is inhibited by Zn2+ and inactivated by Cu2+ and has a pH optimum at around neutrality. Based on the relative values of V(max)/Km, the specificity of the phosphodiesterase toward the four 2',3'-cyclic nucleotides is Guo-2',3'-P > Ado-2',3'-P > Cyd-2',3'-P > Urd-2',3'-P = 45:36:20:7. The enzyme from Artemia gastrulae is competitively inhibited by the four nucleosides 2'-phosphates (Ki values around 1 mM) while the enzyme from larvae is only inhibited by the purine nucleotides. The phosphodiesterase characterized in this work is more similar in substrate specificity to the 2',3'-cyclic nucleotide 3'-phosphodiesterase from the mammalian nervous system than to the plant enzyme. The functional relationship of this enzyme with the Artemia ribonuclease VI is discussed.
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PMID:Purification and characterization of Artemia 2',3'-cyclic nucleotide 3'-phosphodiesterase. 864 16

The allergic pig can be used as a large-animal model for studies of allergic reactions in the airways and the role of eosinophils in such reactions. To measure the activation of eosinophils, the release of eosinophil-derived cationic proteins can be used. The purpose of this study was to isolate and characterize cationic proteins derived from porcine eosinophils. Pigs were infested with live Ascaris suum eggs to induce eosinophilia (greater than or = 40% of leukocytes). Blood was collected and leukocytes were prepared by dextran sedimentation. Granules were obtained from the homogenized leukocytes by ultracentrifugation and cationic proteins were extracted and separated by gel filtration, cation exchange and zinc affinity chromatography. Using these methods, three cationic proteins were isolated from pig granulocytes, two of which were shown to originate from the eosinophil. The proteins were characterized according to molecular weight, amino acid composition, N-terminal sequence, isoelectric point, peroxidase and ribonuclease activity and antigenicity. One eosinophil protein was identified as eosinophil peroxidase and the other showed great similarities with human eosinophil cationic protein. The third protein was not specific for eosinophils, and had no obvious equivalent in human granulocytes. The eosinophil-derived proteins may be useful in the studies of eosinophil activation, e.g. in late-phase asthmatic reactions, where the pig represents a new candidate model for large-animal allergy research.
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PMID:Isolation and characterization of porcine cationic eosinophil granule proteins. 864 90

Large-scale chemical mutagenesis screens in zebrafish have led to the isolation of thousands of lethal mutations in genes that are essential for embryonic development. However, the cloning of these mutated genes is difficult at present as it requires positional cloning methods. In Drosophila, chemical mutagenesis screens were complemented with P-element insertional mutagenesis which facilitated the cloning of many genes that had been identified by chemical lesions. To facilitate the cloning of vertebrate genes that are important during embryogenesis, we have developed an insertional mutagenesis strategy in zebrafish using a retroviral vector. Here, in a pilot screen of 217 proviral insertions, we obtained three insertional mutants with embryonic lethal phenotypes, and identified two of the disrupted genes. One of these, no arches, is essential for normal pharyngeal arch development, and is homologous to the recently characterized Drosophila zinc-finger gene, clipper, which encodes a novel type of ribonuclease. As it is easy to generate tens to hundreds of thousands of proviral transgenes in zebrafish, it should now be possible to use this screening method to mutate and then rapidly clone a large number of genes affecting vertebrate developmental and cellular processes.
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PMID:Insertional mutagenesis and rapid cloning of essential genes in zebrafish. 889 9

An extracellular ribonuclease from Rhizopus stolonifer (designated as RNase Rs) was purified to homogeneity by chromatography on DEAE-cellulose followed by CM-cellulose. The Mr of the purified enzyme determined by gel filtration and SDS-PAGE is 25,000 and 28,200, respectively. RNase Rs is a glycoprotein and contains 10.5% neutral sugar. It is an acidic protein with a pI of 5.0 and has a blocked N-terminus. The optimum pH and temperature are 5.5 and 45 degrees C, respectively. RNase Rs shows high stability between pH 6.0-10.0. Divalent cations like Zn2+, Hg2+ and Cu2+ inhibit the enzyme activity whereas, mononucleotides does not have any significant effect. The enzyme cleaves RNA to 3'-mononucleotides via 2',3'-cyclic nucleotides, with preferential liberation of 2',3'-cyclic GMP, suggesting that RNase Rs is a guanylic acid preferential cyclizing RNase. Moreover, cyclic nucleotides generated are highly resistant to further hydrolysis.
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PMID:Extracellular ribonuclease from Rhizopus stolonifer: characteristics of an atypical--guanylic acid preferential--enzyme from ribonuclease T2 family. 952 62

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that function in the turnover of extracellular matrix components during development. In addition, MMPs also contribute to pathological conditions associated with inflammation, angiogenesis, and tumor invasion. A 72-kDa type IV collagenase, also referred to as gelatinase A or MMP-2, has been proposed to potentiate the invasion and metastasis of malignant tumors. In particular, MMP-2 activity has been shown to constitute an important component of human astroglioma invasion. We investigated the influence of various cytokines, both proinflammatory and immunosuppressive, on MMP-2 gene expression in two human astroglioma cell lines (U251-MG and CRT). Our results indicate that the cell lines constitutively express high levels of MMP-2 mRNA, protein, and bioactivity as assessed by ribonuclease protection assay, immunoblotting, and zymography assays, respectively. The proinflammatory cytokines TNF-alpha and IFN-gamma individually can inhibit constitutive MMP-2 expression, and function in an additive manner for near-complete inhibition of MMP-2 expression. Inhibition of MMP-2 mRNA levels by TNF-alpha and IFN-gamma is not due to destabilization of the MMP-2 message; rather, inhibition is mediated at the transcriptional level. Furthermore, TNF-alpha/IFN-gamma inhibition of MMP-2 expression results in decreased invasiveness of the human astroglioma cells through an extracellular matrix. These results raise the possibility that TNF-alpha and IFN-gamma may have beneficial effects in attenuating astroglioma invasive properties.
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PMID:Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-alpha and IFN-gamma. 986 95

The structure of Bacillus amyloliquefaciens ribonuclease (barnase), an extracellular 110-residue enzyme initially solved at 2.0 A resolution, has been refined at 1.5 A using synchrotron radiation and an imaging-plate scanner. Refinement with anisotropic atomic displacement parameters resulted in increased accuracy of the structure. The final model has a crystallographic R factor of 11.5% and an Rfree of 17.4%. The three independent molecules in the asymmetric unit, referred to as A, B and C, allowed detailed analysis of this final model and meaningful comparison with structures of barnase complexed either with nucleotide inhibitors or with its natural intracellular inhibitor, barstar. The analysis of the overall solvent structure revealed a similar number of water molecules associated with each barnase molecule; among these were 16 equivalent buried solvent molecules, the locations of which are discussed in detail and classified on the basis of their structural role. The importance of the water molecules' contribution to the barnase-barstar interaction is also highlighted. The high accuracy of the present analysis revealed the presence of a Zn2+ ion mediating the contacts between pairs of symmetry-related A, B or C molecules; such an ion had previously only been identified for pairs of C molecules.
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PMID:Refinement and structural analysis of barnase at 1.5 A resolution. 1008 45

We have identified a 30-aa peptide that efficiently cleaves single-stranded RNA. The peptide sequence corresponds to a single zinc finger of the human male-associated ZFY protein; a transcription factor belonging to the Cys(2)His(2) family of zinc-finger proteins. RNA cleavage was observed only in the absence of zinc. Coordination with zinc resulted in complete loss of ribonuclease activity. The ribonuclease active structure was determined to be a homodimeric form of the peptide. Dimerization of the peptide occurred through a single intermolecular disulfide between two of the four cystines. The observed hydrolytic activity was single-stranded RNA-specific. Single-stranded DNA, double-stranded RNA and DNA, and 2'-methoxy-modified sequences were not degraded by the peptide. The peptide specifically cleaved pyrimidines within single-stranded RNA and the dinucleotide sequence 5'-pyr-A-3' was preferred. The RNA cleavage products consisted of a 3' phosphate and 5' hydroxyl. The initial rates of cleavage (V(0)) observed for the finger peptide were comparable to rates observed for human ribonucleases, and the catalytic rate (K(cat)) was comparable to rates observed for the group II intron rybozymes. The pH profile exhibited by the peptide is characteristic of general acid-base catalytic mechanisms observed with other ribonucleases. These observations raise interesting questions about the potential biological roles of zinc-finger proteins.
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PMID:Highly efficient endonucleolytic cleavage of RNA by a Cys(2)His(2) zinc-finger peptide. 1046 53


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