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)

The insulin-like growth factor (IGF)-II/mannose-6-phosphate (M6P) receptor, which targets acid hydrolases to lysosomes, is a multifunctional protein with separate binding sites for IGF-II and M6P. The purpose of this study was to determine if alveolar macrophages (AM) and their precursor cells, blood monocytes, expressed this receptor. AM expressed IGF-II/M6P receptors as detected by [125]IGF-II surface binding that was not reduced by recombinant IGF-I or IGF-I receptor monoclonal antibody (alpha IR3). Surface binding was also detected on blood monocytes and could be upregulated approximately 4-fold by incubation with lipopolysaccharide. There were no differences in surface binding by AM lavaged from individuals with asbestos exposure or from normal volunteers. Using the polymerase chain reaction and reverse transcriptase to reverse-transcribe mRNA from mononuclear phagocytes, specific IGF-II/M6P receptor cDNA was amplified and detected by agarose gel electrophoresis from both AM and blood monocytes. The IGF-II/M6P receptor has an intracellular transport role in many cells cycling from the cell surface to the cytoplasm, or binding to phosphorylated acid hydrolases in the Golgi and transporting them to an acidic prelysosomal site where they dissociate and fuse to the lysosomes and IGF-II/M6P recycles to the trans-Golgi. These functions may be particularly important in asbestosis and other interstitial lung diseases where AM are activated, intracellular lysosomes are a prominent morphologic feature, and acid hydrolases are found in recovered lavage fluid.
Am J Respir Cell Mol Biol 1991 Jun
PMID:Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor. 164 80

The retroid family consists of all genetic elements that encode a potential reverse transcriptase (RT). Members of this family include a diversity of eukaryotic genetic elements (viruses, transposable elements, organelle introns, and plasmids) and the retrons of prokaryotes. Some retroid elements have, in addition to the RT gene, other genes in common with the retroviruses. On the basis of RT sequence similarity, the retroposon group is defined as the eukaryotic long interspersed nuclear elements, the transposable elements of (1) Drosophila melanogaster (I and F factors), (2) Trypanosoma brucei (ingi element), (3) Zea mays (Cin4), (4) Bombyx mori (R2Bm), and members of the group II introns and plasmids of yeast mitochondria. The data presented here elucidate the extent of the relationships between the retroposons and other retroid-family members. Protein-sequence alignment data demonstrate that subsets of the retroposons contain different assortments of retroviral-like genes. Sequence similarities can be detected between the capsid, protease, ribonuclease H, and integrase proteins of retroviruses and several retroposon sequences. The relationships among the retroposon capsid-like sequences are congruent with the RT sequence phylogeny. In contrast, the similarity between ribonuclease H sequences varies in different subbranches of the retroposon lineage. These data suggest that xenologous recombination (i.e., the replacement of a homologous resident gene by a homologous foreign gene) and/or independent gene assortment have played a role in the evolution of the retroposons.
Mol Biol Evol 1991 Nov
PMID:Evolution of retroposons by acquisition or deletion of retrovirus-like genes. 166 70

2',3'-Dideoxyuridine (ddUrd) exhibits poor if any anti-human immunodeficiency virus (HIV) activity in ATH8 and MT-4 cells. This is in agreement with the failure of ddUrd to be efficiently anabolized intracellularly to its 5'-triphosphate metabolite. However, 2',3'-dideoxyuridine-5'-triphosphate (ddUTP) proved to be a potent and selective inhibitor of the reverse transcriptase of HIV (Ki, 0.05 microM) and avian myeloblastosis virus (Ki, 1.0 microM). Bacterial DNA polymerase I, mammalian DNA polymerase alpha, terminal deoxyribonucleotidyl transferase, and Moloney murine leukemia virus reverse transcriptase were resistant to ddUTP. ddUTP is incorporated into the growing DNA chain principally at dTTP sites and inhibits further elongation. The potential of ddUTP as an anti-HIV therapeutic agent merits further investigation. However, to achieve this goal, it will be necessary to resort to techniques capable of delivering preformed phosphorylated ddUrd to the susceptible cells.
Mol Pharmacol 1990 Feb
PMID:Potent DNA chain termination activity and selective inhibition of human immunodeficiency virus reverse transcriptase by 2',3'-dideoxyuridine-5'-triphosphate. 168 52

Approximately 50% of the ribosomal DNA (rDNA) units of Drosophila melanogaster are inactivated by two different 28 S RNA ribosomal gene insertions (type I and type II). We present here the nucleotide sequence of complete type I and type II elements. Conceptual translation of these sequences revealed open reading frames (ORFs) encoding amino acid residues conserved in all retrotransposable elements. Full-length type I elements are 5.35 x 10(3) base-pairs in length and contain two overlapping ORFs. The smaller ORF (471 amino acid residues) has similarity to gag genes, while the larger ORF (1021 residues) has similarity to pol genes. Full-length type II elements are 3.6 x 10(3) base-pairs and contain one large ORF (1056 residues) that appears to represent a gag-pol fusion. Type I and type II elements are similar in structure, in the proteins they encode, and in insertion specificity to the R1Bm and R2Bm retrotransposable elements of Bombyx mori. We suggest that the D. melanogaster elements be called R1Dm and R2Dm, to reflect their structure as retrotransposons. Comparison of the R1 and R2 elements from these two widely different species revealed regions of the ORF that are likely to play an important role in the propagation of the elements. Four distinct regions of sequence conservation separated by regions of little or no sequence similarity were detected for both the R1 and R2 elements: (1) cysteine motifs of the gag gene, with three such motifs for R1 and one motif for R2; (2) a reverse transcriptase domain; (3) an integrase domain located carboxyl terminal to the reverse transcriptase region; and (4) a small region amino terminal to the reverse transcriptase domain, whose function is not known. The level of identity of the amino acid residues for these segments is 28 to 34% between the R1 elements, and 34 to 39% for the R2 elements. Finally, it may be predicted that the mechanism of unequal crossover might eventually eliminate R1 and R2 from the rDNA locus. The long history of selection at the protein level exhibited by these elements indicates that it is their active transposition that maintains them in the locus. The high level of sequence homogeneity between copies of each element within the same species is consistent with the high turnover rate expected to result from these processes.
J Mol Biol 1990 Mar 05
PMID:Type I (R1) and type II (R2) ribosomal DNA insertions of Drosophila melanogaster are retrotransposable elements closely related to those of Bombyx mori. 169 Aug 12

Ribonuclease and chemical probes were used to investigate the binding sites of ribosomal protein L11 and the pentameric complex L10.(L12)4 on Escherichia coli 23 S RNA. Protein complexes were formed with an RNA fragment constituting most of domains I and II or with 23 S RNA and they were investigated by an end-labelling method and a reverse transcriptase procedure, respectively. The results demonstrate that the two protein moieties bind at adjacent sites within a small RNA region. The L11 binding region overlaps with those of the modified peptide antibiotics thiostrepton and micrococcin and is constrained structurally by a three-helix junction while the L10.(L12)4 site is centred on an adjacent internal loop. The secondary structure of the whole region was determined in detail by the phylogenetic sequence comparison method, and the results for the L11 binding region, together with the experimental data, were used in a computer graphics approach to build a partial RNA tertiary structural model. The model provides insight into the topography of the L11 binding site. It also provides a structural rationale for the mutually co-operative binding of protein L11 with the antibiotics thiostrepton and micrococcin, and with the L10.(L12)4 protein complex.
J Mol Biol 1990 May 20
PMID:Characterization of the binding sites of protein L11 and the L10.(L12)4 pentameric complex in the GTPase domain of 23 S ribosomal RNA from Escherichia coli. 169 83

A single copy of the retrotransposon TED, from the moth Trichoplusia ni (a lepidopteran noctuid), was identified within the DNA genome of the baculovirus Autographa californica nuclear polyhedrosis virus. Determination of the complete nucleotide sequence (7,510 base pairs) of the integrated copy indicated that TED belongs to the family of retrotransposons that includes Drosophila melanogaster elements 17.6 and gypsy and thus represents the first nondipteran member of this invertebrate group to be identified. The internal portion of TED, flanked by long terminal repeats (LTRs), is composed of three long open reading frames comparable in size and location to the gag, pol, and env genes of the vertebrate retroviruses. Sequence similarity with the dipteran elements was the highest within individual domains of TED open reading frame 2 (pol region) that are also conserved among the retroviruses and encode protease, reverse transcriptase, and integrase functions, respectively. Mapping the 5' and 3' termini of TED RNAs indicated that the LTRs have a retroviral U3-R-U5 structural organization that is capable of directing the synthesis of transcripts that represent potential substrates for reverse transcription and intermediates in transposition. Abundant RNAs were also initiated from a site within the 5' LTR that matches the consensus motif for the promoter of late, hyperexpressed baculovirus genes. The presence of this viruslike promoter within TED and its subsequent activation only after integration within the viral genome suggest a possible symbiotic relationship with the baculovirus that could extend transposon host range.
Mol Cell Biol 1990 Jun
PMID:Gene organization and transcription of TED, a lepidopteran retrotransposon integrated within the baculovirus genome. 169 64

Rubromycins, a class of quinone antibacterials, were discovered to selectively inhibit human immunodeficiency virus-1 (HIV-1) RNA-directed DNA polymerase (reverse transcriptase) (RT) activity more potently than cellular DNA polymerase alpha. beta- and gamma-rubromycin each inhibited equipotently HIV-1 RT and avian myeloblastosis virus RT, in a concentration-dependent manner, and were significantly weaker as inhibitors of calf thymus DNA polymerase alpha. These agents inhibited HIV-1 RT reversibly, were competitive with respect to template.primer, and were noncompetitive with respect to TTP. Dixon analyses yielded HIV RT Ki values of 0.27 +/- 0.014 and 0.13 +/- 0.012 microM for beta- and gamma-rubromycin, respectively. Similarly, using DNA polymerase alpha, the Ki values were 25.1 +/- 4.3 and 3.9 +/- 0.6 microM for beta- and gamma-rubromycin, respectively. Because these agents were toxic to noninfected human T lymphoid cells using concentrations at or above 6 microM, HIV-1 infectivity studies were carried out at 0.8-6 microM. At these concentrations, which are below the range expected to provide protection, no significant antiviral activity was observed. Although beta- and gamma-rubromycins did not possess sufficient HIV RT inhibitory potency or selectivity versus mammalian DNA polymerase to demonstrate antiviral activities, these studies support the hypothesis that specific molecules containing quinone functional groups can selectively inhibit viral polymerase activities over cellular polymerase activities. In addition, these studies suggest that rubromycins may be lead structures for the development of more potent and selective agents.
Mol Pharmacol 1990 Jul
PMID:Inhibition of human immunodeficiency virus-1 reverse transcriptase activity by rubromycins: competitive interaction at the template.primer site. 169 17

The yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe transformed by plasmids containing retrotransposon from yeast or Drosophila under the control of a strong promoter show the remarkable reverse transcriptase activity. The activity results in the impaired yeast growth and decreased mitotic stability of the plasmids. The phenotypic expression of the reverse transcriptase activity is observed within 30 days.
Mol Gen Mikrobiol Virusol 1990 Aug
PMID:[Phenotypic manifestations of reverse transcriptase activity in yeast cells]. 170 Feb 91

Ribavirin inhibits the human immunodeficiency virus reverse transcriptase in an in vitro reaction. Ribavirin-5'-diphosphate was close to 40% more inhibitory than ribavirin-5'-triphosphate. Unphosphorylated ribavirin had a reduced, but detectable, effect as an inhibitor, compared with the phosphorylated forms. The compounds seem to have a direct effect on the viral polymerase, and no chain termination was observed in the presence of ribavirin-5'-triphosphate. Combination of any of the ribavirin derivatives tested with 3'-azido-3'-deoxythymidine (zidovudine)-5'-triphosphate resulted in an increase of its anti-human immunodeficiency virus reverse transcriptase activity in the in vitro assay.
Mol Pharmacol 1990 Dec
PMID:Ribavirin is an inhibitor of human immunodeficiency virus reverse transcriptase. 170 Dec 13

The comparison of the Km and vmax values for various primers was carried out. The primers were either completely complementary to the poly(A)-template or contained noncomplementary bases in different positions from the 3'-end. An increase of the Km and vmax values for primers containing noncomplementary bases was shown. The affinity of the AMV-revertase complex with poly(A)-template to d(pT)10 was shown to be higher by a factor of 93, 325, 338, 425, 95 and 15 than to d(pT)9(pC), d[(pT)2pC]3pT, d(pT)8pCpT, d(pT)7pC(pT)2, d(pT)4pC(pT)5 and d(pC)3(pT)7, respectively. The vmax values for the above primers were 1.2-1.5-fold higher than for d(pT)10. The decrease of the affinity of noncorrect primers to the enzyme was supposed to serve as a mechanism for mistakes correction when noncomplementary to the template mononucleotide units were added to the primer. More effective discrimination between right and wrong primers takes place if the noncomplementary base is in the second or third position from the 3'-end. The mistake correction is performed by dissociation of a wrong primer from the complexes with the enzyme and template. The data obtained for AMV-revertase are in accord with results for pro- and eukaryotic DNA polymerases and are in favour of a similar mechanism of mistake correction by all enzymes in the case of short primers.
Mol Biol (Mosk)
PMID:[The effect of bases noncomplementary to the template on the effectiveness of interaction between primers and avian myeloblastosis virus reverse transcriptase]. 170 Dec 18


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