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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some 37 reverse transcriptase, partial 16S rRNA sequences from sulfur- and/or iron-oxidizing eubacteria, including sequences from species of the genera Thiobacillus, Thiothrix, Thiomicrospira, Acidophilium, "Leptospirillum," Thiovulum, and Chlorobium, have been determined. In addition, 16S sequences from a number of unnamed sulfur- and/or iron-oxidizing bacteria from hydrothermal vent sites, from invertebrate-bacterial endosymbioses, and from various mineral recovery operations also have been determined. The majority of sequences place their bacterial donors in one or another of the subdivisions of the Proteobacteria. However, three unnamed facultatively thermophilic iron-oxidizing isolates, Alv, BC, and TH3, are affiliated with the gram-positive division. One H2S-oxidizer, from the genus Thiovulum, is affiliated with Campylobacter, Wolinella, and other genera in what appears to be a new subdivision of the Proteobacteria. Three "Leptospirillum"-helical vibrioid isolates, BU-1, LfLa, and Z-2, exhibit no clear phylum level affiliation at all, other than their strong relationship to each other. A picture is emerging of an evolutionary widespread capacity for sulfur and/or iron oxidation among the eubacteria.
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PMID:Evolutionary relationships among sulfur- and iron-oxidizing eubacteria. 172 14

RNA tumor viruses contain a characteristic RNA-dependent DNA polymerase (reverse transcriptase) which has been thought to be related to the induction of leukemia by this virus. A disturbance in a zinc-dependent enzyme system was first postulated to account for the demonstrated differences in zinc metabolism of normal and leukemic leukocytes [Vallee et al. in (1949) Acta Unio. Int. Contra Cancrum 6, 869 and (1950) Acta Unio. Int. Contra Cancrum 6, 1102]. In order to investigate the relationship between zinc and the initiation of leukemia in chickens by avian myeloblastosis virus, we have examined the metalloenzyme nature of its reverse transcriptase. The present data show that this protein is a zinc metalloenzyme demonstrating the postulated relationship between zinc and a leukemic process. Paucity of purified enzyme generated the design of a novel system of analysis incorporating microwave-induced emission spectrometry combined with gel exclusion chromatography. It provides precision, reproducibility, and remarkable limits of detection on mul samples containing 10(-12) to 10(-14) g-atoms of metal, and is thus orders of magnitude more sensitive than other methods. The chromatographic fraction with highest enzymatic activity contains 1.8 x 10(-11) g-atoms of zinc per 1.6 mug of protein, corresponding to either 1.8 or 2.0 g-atoms of zinc per mole of enzyme for a molecular weight previously determined either as 1.6 or 1.8 x 10(5). Copper, iron and manganese are absent, i.e., at or below the limits of detection, 10(-13) to 10(-14) g-atoms. Agents known to chelate zinc inhibit the enzyme, while their nonchelating isomers do not. The data underline the participation of zinc in nucleic acid metabolism and bear importantly upon the lesions that accompany leukemia and zinc deficiency.
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PMID:RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus: a zinc metalloenzyme. 413 17

The ability of iron(II).bleomycin to mediate RNA degradation was further characterized. At micromolar concentrations, FeII.BLM was shown to effect cleavage of Escherichia coli tRNA(1His) and a Schizosaccharomyces pombe amber suppressor tRNA construct in an efficient fashion. In contrast, E. coli tRNA(Cys) and yeast mitochondrial tRNA(Asp) and tRNA(fMet) precursors were not substrates for FeII.BLM. Also shown to be a good substrate for cleavage by FeII.BLM was yeast 5S ribosomal RNA. Since HIV-1 reverse transcriptase mRNA has previously been shown to be degraded by Fe.BLM (Carter et al., 1990a), members of the three major classes of RNA have now been shown to undergo Fe.BLM-mediated strand scission. For each of the substrate RNAs, cleavage occurred at sites unique to that substrate. Although RNA cleavage occurred at numerous sequences, 5'-G-pyr-3' sites were prominent. Likewise, while cleavage was noted in regions anticipated to be double-stranded, as well as in single-stranded regions, a disproportionate number of cleavages were noted at the junction between single- and double-stranded regions. As found in earlier studies, RNA cleavage was much more selective than DNA cleavage. Further, when RNA cleavage was carried out in the presence of reagents such as Mg2+, spermidine, and NaCl, the selectivity of cleavage was further enhanced. The highly selective and efficient cleavage of a number of RNA molecules reinforces our earlier suggestion that RNA may constitute a therapeutically relevant target for bleomycin.
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PMID:Characterization of iron (II).bleomycin-mediated RNA strand scission. 768 45

The full length copy DNA (cDNA) for human lactoferrin has been synthesised by the polymerase chain reaction (PCR) using sequence specific primers. The template was first strand cDNA, synthesised from human bone marrow RNA using oligo(dT) to prime DNA synthesis by MMLV reverse transcriptase. The full-length human lactoferrin cDNA has been expressed in baby hamster kidney (BHK) cells using the expression vector pNUT. The protein expressed from the cloned cDNA is secreted into the culture medium and yields of up to 40 mg per litre have been obtained. A mutant protein corresponding to the N-lobe of human lactoferrin (LfN) has also been expressed in BHK cells. The cDNA coding for this protein was produced by the introduction of stop codons into the region of the cDNA corresponding to the helix linking the N- and C-lobes of the native protein. LfN is also expressed as a secreted protein and has been obtained in high yield. LfN binds iron and has UV/Vis and ESR spectra which are virtually identical to the native protein. However, the pH at which iron is released from LfN is quite different to the pH of iron release from the native and the full-length recombinant protein. A number of mutations have been introduced into LfN by site-directed mutagenesis and the mutant proteins expressed in BHK cells. These mutations involve the iron binding ligands and have been designed to introduce some of the changes found in the C-lobe of melanotransferrin into LfN. An attempt has been made to express a protein corresponding to the C-lobe of human lactoferrin (LfC) by attaching the sequence for the signal peptide of lactoferrin to the cDNA sequences coding for the C-lobe.
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PMID:Lactoferrin cDNA. Expression and in vitro mutagenesis. 776 31

An important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) through redox-controlled signal transduction pathways. In this study, we demonstrate that iron chelation by deferoxamine (DFO) protects against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). These protective effects were observed both in lymphocytic (ACH-2) and promonocytic (U1) cells latently infected by HIV-1. Concomitantly, NF-kappa B activation by H2O2, when followed by gel retardation assay, was decreased in the DFO-treated U1 and ACH-2 cells. This latter DFO-mediated effect was specific, as DFO did not clearly affect AP-1 DNA-binding activity when studied after H2O2-induced stress. More importantly, DFO protected against the H2O2-induced activation of HIV-1 as evidenced by reverse transcriptase activity in the supernatant. DFO also protected against PMA-induced NF-kappa B activation as well as TNF-alpha-induced HIV-1 activation. Furthermore, DFO attenuated the p24 response in PBMC infected with HIV-1 and stimulated with IL-2. These different effects of DFO were obtained at DFO concentrations lower than 5 microM. Other chemically unrelated iron chelators also provided protection against cytotoxicity, NF-kappa B activation, and HIV-1 activation in U1 cells challenged with H2O2.
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PMID:Iron chelation decreases NF-kappa B and HIV type 1 activation due to oxidative stress. 855 2

A cDNA encoding full-length tryptophan hydroxylase was produced by reverse transcriptase-PCR from rat brain mRNA and expressed transiently in a human fibroblast cell line. Catalytic activity was low unless transfected cells were grown in the presence of FeSO4. Recombinant tryptophan hydroxylase was found almost exclusively within the soluble compartment of the cell and was dependent on tryptophan and tetrahydrobiopterin for activity. The catalytic activity of recombinant tryptophan hydroxylase was stimulated > 25-fold by Fe(II) and to a somewhat lesser extent by the polyanions heparin and phosphatidylserine. The enzyme was inhibited by desferrioxamine and dopamine, both of which complex iron. When extracts from transfected cells were subjected to sucrose gradient centrifugation and analytical gel filtration, the recombinant enzyme behaved the same as the native enzyme from brain. A monoclonal antibody against phenylalanine hydroxylase that cross-reacts with brain tryptophan hydroxylase was capable of immunoprecipitating the recombinant hydroxylase from solution. These data indicate that recombinant tryptophan hydroxylase expressed in mammalian cells is assembled into tetramers of approximately 220,000 daltons. Its catalytic and physical properties appear to be very similar to those of the native enzyme from brain.
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PMID:Tryptophan hydroxylase: cloning and expression of the rat brain enzyme in mammalian cells. 875 94

Pathological changes arising in altered cell biology and diseases such as cancer are driven by changes in gene expression. In the inherited disease haemochromatotis (HC) progressive iron loading of the parenchymal cells (hepatocytes) of the liver leads to cellular toxicity. If left untreated, fibrosis, cirrhosis and ultimately liver cancer occur. By using differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) techniques, we have identified and isolated several differentially displayed mRNAs that are excessively expressed or repressed in HC liver compared to normal human liver. One of these mRNAs was found to be strongly expressed in the liver of a patient with HC and in tumour tissue from a subject with hepatocellular carcinoma complicating HC (HC/HCC). The message of this gene was detected at a very low level in normal human liver. Northern analysis showed that this gene is also expressed in lymphocytes of HC patients and in MOLT-4 human T-lymphoid cells irrespective of iron status. The partial 1.0 kb cDNA sequence of the 9.5 kb transcript of this gene is unique and we propose that this gene may be related to cell proliferation and HC/HCC human liver.
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PMID:Molecular cloning of a novel mRNA highly expressed in haemochromatotic human liver and proliferating cells. 880 57

We have characterized a 5.2-kilobase (kb) putative transport related operon (tro) locus of Treponema pallidum subsp. pallidum (Nichols strain) (Tp) encoding six proteins: TroA, TroB, TroC, TroD, TroR and Phosphoglycerate mutase (Pgm). Four of these gene products (TroA-TroD) are homologous to members of the ATP-Binding Cassette (ABC) superfamily of bacterial transport proteins. TroA (previously identified as Tromp1) has significant sequence similarity to a family of Gram-negative periplasmic substrate-binding proteins and to a family of streptococcal proteins that may have dual roles as substrate binding proteins and adhesins. TroB is homologous to the ATP-binding protein component, whereas TroC and TroD are related to the hydrophobic membrane protein components of ABC transport systems. TroR is similar to Gram-positive iron-activated repressor proteins (DesR, DtxR, IdeR, and SirR). The last open reading frame (ORF) of the tro operon encodes a protein that is highly homologous to the glycolytic pathway enzyme, Pgm. Primer extension results demonstrated that the tro operon is transcribed from a sigma 70-type promoter element. Northern analysis and reverse transcriptase-polymerase chain reactions provided evidence for the presence of a primary 1-kb troA transcript and a secondary, less abundant, troA-pgm transcript. The tro operon is flanked by a Holliday structure DNA helicase homolog (upstream) and two ORFs representing a purine nucleoside phosphorylase homolog and tpp15, a previously characterized gene encoding a membrane lipoprotein (downstream). The presence of a complex operon containing a putative ABC transport system and a DtxR homolog indicates a possible linkage between transport and gene regulation in Tp.
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PMID:Identification and transcriptional analysis of a Treponema pallidum operon encoding a putative ABC transport system, an iron-activated repressor protein homolog, and a glycolytic pathway enzyme homolog. 933 49

Ferritin is a ubiquitous protein which plays a major role in iron sequestration, detoxification and storage. In this paper we highlight the role of ferritin in iron homeostasis and describe factors and diseases that affect its expression. We also describe new studies which further characterize the structure and expression of a novel form of ferritin heavy (H) chain mRNA that was identified in brain and discuss possible implications of these findings. Human fetal and adult brain cDNA libraries previously were screened with cDNA for well-characterized liver ferritin H. In addition to 'liver-like' brain ferritin H cDNA, novel ferritin H cDNAs with an additional 279 nucleotide sequence at the 3'untranslated region (UTR) were identified in both libraries (see refs. 1 and 2; Dhar, M., Chauthaiwale, V., and Joshi, J. G., Gene, 1993, 126, 275 and Dhar, M., and Joshi, J. G., J. Neurochem., 1993, 61, 2140). However, relative to liver ferritin H cDNA, these novel cDNAs were incomplete at their 5'ends [see ref. 3; Joshi, J. G., Fleming, J. T., Dhar, M. S., and Chauthaiwale, V., J. Neurol Sci., 1995, 134, (Suppl.), 52]. In the present paper, by sequencing of cDNAs using reverse transcriptase polymerase chain reaction, we show that the 279 nt 3'UTR sequence, a coding sequence identical to that in human liver ferritin H, and a full-length 5'UTR that includes one mRNA regulatory iron-response element sequence, co-exist in at least one species of ferritin H transcript in six normal human adult and six late-onset, sporadic Alzheimer disease (AD) brains. This sequence is the same in the normal and AD brains. Dot-blot analysis of poly A+ RNAs from different human tissues indicates that relative to the coding sequence of ferritin H, expression of the 279 nt 3'UTR sequence varies among different tissues, is highest in the adult brain, and is very low in fetal brain. In normal adult hippocampus, ferritin H RNA with the novel 279 nt sequence localizes strongly to small non-neuronal cells, capillary endothelial cells, and to selected populations of neurons (granule cells of the dentate gyrus). Significant homology was observed between a region in the 279 nt 3'UTR segment of ferritin H RNA and the 3'UTR of cyclooxygenase-2 mRNA (an inducible iron-containing enzyme involved in prostaglandin synthesis). Possible functions for ferritin H protein derived from the novel message and for the elongated 3'UTR and 5'UTR are discussed.
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PMID:Iron metabolism and human ferritin heavy chain cDNA from adult brain with an elongated untranslated region: new findings and insights. 958 Oct 19

Exposure to mineral dusts is associated with the development of chronic airflow obstruction, probably mediated in part by dust-induced fibrosis of the small airways. To investigate the mechanism of fibrosis, we exposed rat tracheal explants to amosite asbestos, iron oxide, or titanium dioxide. Explants were then maintained in air organ culture, and the expression of genes encoding for various mediators and matrix components assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). At 7 d, all dusts produced significant increases in platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta1 (TGF-beta1) gene expression compared with control; asbestos and titanium dioxide produced increases in PDGF-B, and titanium dioxide increased TGF-alpha expression. Only asbestos caused increases in procollagen expression. No dust increased expression of tumor necrosis factor-alpha (TNF-alpha), fibronectin, or tropoelastin. Elevations in these factors coincided temporally with transport of particles into the epithelium and then to the subepithelial space. By in situ hybridization, TGF-beta gene expression was found in both the epithelium and subepithelial (interstitial) space, and PDGF-B and procollagen gene expression in the subepithelial space. Chemical analysis showed a small increase in hydroxyproline, a measure of collagen content, in asbestos-treated explants. We conclude that mineral dusts can induce airway wall fibrosis by directly upregulating proliferative and fibrogenic mediators as well as matrix components in the airway epithelium and interstitium, and that neither airspace nor circulating inflammatory cells are required for these effects. Different mineral dusts produce different patterns of reaction.
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PMID:Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall. 984 85


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