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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alkoxybenzophenanthridine alkaloids (coralyne acetosulfate, fagaronine chloride, and nitidine chloride) have been reported to possess antileukemic activity in mice. These compounds were tested for inhibition of reverse transcriptase activity of an RNA tumor virus and DNA polymerase, RNA polymerase, and polyadenylic acid polymerase activities of NIH-Swiss mouse embryos. Reverse transcriptase and DNA polymerase activities were strongly inhibited by these antileukemic alkaloids, whereas RNA polymerase and polyadenylic acid polymerase activities were only moderately affected. Viral and cellular DNA polymerase activities were potently diminished by the alkaloids when poly[d(A-T)], poly(dA)-oligo(dT), and poly(rA)-oligo(dT) template primers were used in the reaction mixture; however, no inhibition of enzyme activity was obtained with poly(rC)-oligo(dG) as template primer. These results suggest that alkoxybenzophenanthridine alkaloids inhibit DNA polymerase activity by interaction with A:T base pairs of the template primer.
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PMID:Inhibition of mammalian and oncornavirus nucleic acid polymerase activities by alkoxybenzophenanthridine alkaloids. 5 19

Reverse transcriptase activity was detected in the supernatants of rat embryo fibroblast cell cultures transformed by HSV types 1 and 2 at either the sub-optimal temperature of 20 degrees C or the supra-optimal temperature of 42 degrees C. Rat cells clones which had been transformed at 20 degrees C contained higher levels of C-type virus DNA polymerase than did cell clones which had been transformed at 42 degrees C. Syncytia formation typical for C-type RNA viruses occurred at passages higher than 24. The activation of endogenous C-type RNA viruses was independent of the virus and transformation method used.
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PMID:Activation of an endogenous C-type RNA virus in rat embryo cells after transformation by herpes simplex virus types 1 and 2. 7 May 8

Samples of three nonmalignant and seven leukemic human cells were examined for DNA polymerase activity that could be identified as RNA tumor virus reverse transcriptase. Experiments on virus-infected model animal cells provided the basis for cell fractionation procedures, and reconstituted systems of known virus, added to human cells, established a threshold of virus detection by enzyme assay at 1 to 10 particles/cell. DNA polymerase activity with some properties similar to a reverse transcriptase was detected in some of the human leukemic cells. However, parallel analyses of nonmalignant cells showed sufficient similarities to raise serious questions about the specificity of the criteria. Reverse transcriptase activity has been reported to be present in white blood cells from a proportion of cases of leukemia; however, it is concluded from the present study that the usual enzymatic criteria using synthetic template primers, which were used in most of the studies reported, are not sufficient to identify a DNA polymerase activity as viral reverse transcriptase.
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PMID:Detection of reverse transcriptase activity in human cells. 8 60

The inhibitor sensitivity and functional domains of recombinant encephalomyocarditis (EMC) virus RNA-dependent RNA polymerase (3Dpol) have been extensively analyzed. The inhibitor profiles of EMC virus 3Dpol and Escherichia coli DNA-dependent RNA polymerase are distinct, and experiments with substrate analogs indicate that EMC virus 3Dpol lacks reverse transcriptase activity. Twenty amino acid substitutions were engineered in EMC virus 3Dpol based on sequence alignments of viral RNA-dependent RNA polymerases that identified conserved amino acid residues within motifs. Ten out of 17 conservative substitutions within the four most conserved motifs reduced the RNA polymerase activity of the mutants to 0-6% of the activity of the wild-type enzyme, demonstrating the importance of these amino acids in the structure and/or function of EMC virus 3Dpol. Remarkably, 5 of the 10 mutations in EMC virus 3Dpol which had the most drastic effect on its RNA polymerase activity (D240E, S293T, N302Q, G332A, and D333E) were found to correspond to active site residues in E. coli DNA-dependent DNA polymerase I (Klenow). Our results reveal that a basic structural and functional framework is conserved in the most distantly related classes of nucleic acid polymerases and demonstrate the validity of modeling the active site of an RNA-dependent RNA polymerase on the known structure of a DNA polymerase.
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PMID:Point mutations which drastically affect the polymerization activity of encephalomyocarditis virus RNA-dependent RNA polymerase correspond to the active site of Escherichia coli DNA polymerase I. 131 53

Although the origin of viruses has not yet been clarified, definite differences in evolutionary patterns have been found among RNA. Retro and DNA viruses. These differences are reflected in infectious diseases. RNA viruses, which have RNA in their genome, replicate many times over in cells within a short period of time, destroying the host cells and causing an acute infection. As the error frequency of RNA replicase enzymes is high, the rate of evolution of RNA viruses is very rapid. Retroviruses also contain RNA as their genome, but the genome RNA is reversely transcribed to the DNA in nuclei and then incorporated into the host chromosome to replicate. The error frequency of reverse transcriptase is also high, and therefore mutations easily occur as well. The transcribed DNA is integrated into host DNA in the nucleus, and it remains in the integrated state for human entire life time, causing chronic disease or developing malignant tumors. As DNA viruses except poxviruses replicate inside the cell nucleus and the error frequency of DNA polymerase is low, the speed of mutation and the degree of resulting diversity are lower than those in the case of the RNA virus. DNA viruses tend to stay inside the body for long periods of time and easily become latent. In this paper, I shall discuss 1) the nature of viruses, 2) the origin of viruses, 3) mutation and recombination, 4) diversity of RNA viruses, 5) quickly changing viral diseases, 6) eradicated viral diseases, 7) chronic and malignant diseases, and 8) control of viral diseases.
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PMID:[Evolution and ecological changes of animal viruses]. 140 23

Reverse transcriptase (RT) plays an essential role in the life cycle of the human immunodeficiency viruses (HIV). A better understanding of this enzyme, and its two catalytic functions, the DNA polymerase and the RNase H, could lead to the development of new drugs that would specifically block HIV replication. The available genetic, sequence, biochemical, and immunological data on the reverse transcriptase of HIV-1 constrain the possible structure of the DNA polymerase domain. The purpose of this review is to correlate the data and to discuss, in light of that data, a model for the structure of the polymerase domain. In this model, the polymerase domain is approximately 50 to 60 A in diameter with a 20 A opening to accommodate the nucleic acid duplex. The most evolutionarily conserved region of RT (amino acids 20-190 of HIV-1 RT) is proposed to form the inner surface of the 20 A opening to which the nucleic acid hemiduplex is bound.
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PMID:HIV-1 reverse transcriptase: structure predictions for the polymerase domain. 170 98

2-Chloro-2'-deoxyadenosine 5'-triphosphate (CldATP) was compared with dATP as a substrate for DNA synthesis by bacterial and viral DNA polymerases in vitro. Lengths of chain extension and DNA synthesis pause sites were determined by comparison with products generated by dideoxynucleotide sequencing methods on the same end-labeled primer/template duplex after high-resolution polyacrylamide gel electrophoresis. Reverse transcriptase (RT) from human immunodeficiency virus (HIV-1) and avian myeloblastosis virus (AMV) incorporated CldATP efficiently. DNA strand elongation continued past most chloroadenine (ClA) insertion sites but resulted in shorter chains than when dATP was inserted. Phage T4 DNA polymerase incorporated CldATP least efficiently; Klenow fragment of Escherichia coli DNA polymerase I and modified T7 DNA polymerase (Sequenase) showed intermediate ability to utilize the analogue. Incorporation of several consecutive ClA residues into the replicating strand dramatically reduced the ability of Sequenase, Klenow fragment, and T4 DNA polymerases to continue strand elongation. In the absence of the corresponding normal deoxyribonucleoside triphosphate during DNA synthesis, ClA was frequently misincorporated as thymine, cytosine, or guanine by both AMV RT and HIV-1 RT but rarely, if at all, by Klenow fragment, Sequenase, and T4 DNA polymerase. Except T4, for most DNA polymerases, CldATP at 10-20-fold molar excess over dATP was not a strong competitive inhibitor of dATP, as judged by the amount of strand extension and polymerase pause sites during DNA synthetic reactions. Our results indicate that the degree of strand extension in the presence of CldATP, the number and location of polymerase pause sites, and the amount of misincorporation of the analogue are both polymerase- and sequence-dependent.
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PMID:Effects of 2-chloro-2'-deoxyadenosine 5'-triphosphate on DNA synthesis in vitro by purified bacterial and viral DNA polymerases. 170 19

A primase-reverse-transcriptase of Halobacterium halobium was purified by column chromatography on DEAE-cellulose, hydroxyapatite and carboxymethyl-cellulose, followed by sedimentation on a glycerol gradient. The enzyme is a multifunctional enzyme containing reverse transcriptase. DNA polymerase and RNase H activities and does not require a performed primer to initiate DNA synthesis. Using a single-stranded DNA as template, this enzyme synthesizes oligonucleotides (8-12 bases) that can be used a primer by Escherichia coli DNA nucleotidyltransferase I (DNA polymerase I, Klenow fragment). Two polypeptides of 67 and 57 kDa were found after 14750-fold purification of the enzyme.
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PMID:Reverse transcriptase in archaebacteria. Purification and characterization of a primase-reverse-transcriptase complex from Halobacterium halobium. 170 56

We have amplified herpes simplex virus type 1 (HSV-1) DNA sequences from individual latently infected mouse trigeminal ganglia by polymerase chain reaction (PCR) assays. This report presents two useful modifications in the PCR technique. The first involves the use of two sets of closely spaced, oppositely oriented oligonucleotide primers and two rounds of 20-40 PCR cycles, first with the more widely spaced outer primers and then with the internal nested primers. This method enhanced the sensitivity of PCR detection as shown by assays of HSV-1 sequences in human brain. The second modification was designed to detect selectively HSV-1 sense or anti-sense RNA transcripts when both are present by adding a single primer during an initial reverse-transcriptase-mediated cDNA synthesis reaction. After destruction of the RNA template, standard PCR is initiated by the addition of the second primer and thermus aquaticus DNA polymerase (Taq). We show here applications of both of these modifications to amplify HSV-1 sequences from nervous system tissue.
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PMID:Application of polymerase chain reaction assays to studies of herpes simplex virus latency. 185 Nov 47

5-(Phosphonomethyl)-1H-tetrazole and a number of related tetrazoles have been prepared and their effects on the replication of Herpes Simplex Viruses-1 and -2 have been investigated as well as their abilities to inhibit the DNA polymerases induced by these viruses and the RNA transcriptase activity of influenza virus A. Contrary to an earlier report, 5-(phosphonomethyl)-1H-tetrazole was not an efficient inhibitor of the replication of HSV-1 and HSV-2 in tissue culture. Analogues of 5-(phosphonomethyl)-1H-tetrazole were also devoid of significant antiviral activity. Only 5-(phosphonomethyl)-1H-tetrazole and 5-(thiophosphonomethyl)-1H-tetrazole inhibited the influenza virus transcriptase, and both were more effective as inhibitors than phosphonoacetic acid under the same conditions. The DNA polymerases induced by HSV-1 and HSV-2 were inhibited slightly by 5-(phosphonomethyl)-1H-tetrazole and to a lesser extent by its N-ethyl analogue and 3-(phosphonomethyl)-1H-1,2,4-triazole. None of these compounds were as effective as phosphonoacetic acid. 5-(Thiophosphonomethyl)-1H-tetrazole was a better inhibitor of the DNA polymerase induced by HSV-1 than 5-(phosphonomethyl)-1H-tetrazole.
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PMID:The antiviral activity of tetrazole phosphonic acids and their analogues. 241 98


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