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:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polymer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT (reverse transcriptase) and the drug possesses excellent antiviral activity at nontoxic doses in HIV-infected lymphocytes grown in tissue culture. The drug also inhibits RTs isolated from other species such as AMV and MLV retroviruses. Enzymatic kinetic studies of the HIV-1 RT catalyzed RNA-directed DNA polymerase function, using synthetic template:primers, indicate that the drug acts generally noncompetitively with respect to the template:primer binding site but the specific inhibition patterns change somewhat depending on the drug concentration. The inhibitor acts noncompetitively with respect to the dNTP binding sites. Hence, the drug inhibits this RT polymerase function by interacting with a site distinct from the template:primer and dNTP binding sites. In addition, the inhibitor also impairs the DNA-dependent DNA polymerase activity of HIV-1 RT and the RNase H function. This indicates that the drug interacts with a target site essential for all three HIV RT functions addressed (RNA- and DNA-directed DNA polymerases, RNase H).
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PMID:Enzymatic kinetic studies with the non-nucleoside HIV reverse transcriptase inhibitor U-9843. 128 6

The mobile element jockey is similar in structural organization and coding potential to the LINEs of various organisms. Current models of the mechanism of transposition involve reverse transcription of an RNA intermediate and utilization of element-encoded proteins. As it is demonstrated here, a 2.23 kb DNA fragment from the region of the jockey encoding the putative reverse transcriptase, was stably introduced into the expression system under inducible control of the Escherichia coli lac regulatory elements. We describe the expression of the 92 kDa protein and identify this polypeptide alone as authentic jockey reverse transcriptase based on some of its physical and enzymic properties. The jockey polymerase demonstrates RNA-directed and DNA-directed DNA polymerase activities, but lacks detectable RNase H, has a temperature optimum at 26 degrees C, requires Mg2+ or Mn2+ as a cofactor and is inactivated by sulfhydryl reagent. The enzyme prefers poly(rC) and poly(rA) as template and "activated" DNA is not effective. The results of this work suggest that the RNA-directed DNA polymerase coded by jockey elements may be involved in the transcription of the elements.
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PMID:[Cloning and expression in Escherichia coli of reverse transcriptase coded by the mobile genetic element jockey]. 138 Jun 45

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.
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PMID:Inhibition of human immunodeficiency virus-1 reverse transcriptase activity by rubromycins: competitive interaction at the template.primer site. 169 17

Enzymological properties of the RNA-directed DNA polymerase associated with the Suncus murinus mammary tumor virus (Sm-MTV) was investigated and its antigenic relatedness to other retroviral DNA polymerases was examined. The enzyme exhibited higher activity in the presence of Mg2+ than in the presence of Mn2+ with endogenous RNA as well as with almost all of the synthetic template X primers tested. Mg2+ was also effective with poly(2'-O-methylcytidylate) X oligodeoxyguanylate which was known to be specific for Mn2+. To examine the immunological relatedness of this enzyme with other retroviral DNA polymerases, remaining Sm-MTV DNA polymerase activity was measured after treatment of this enzyme with various antisera prepared against each of the reverse transcriptases of Mason-Pfizer monkey virus (MPMV), murine mammary tumor virus (MuMTV), simian sarcoma virus-simian sarcoma associated virus (SSV/SSAV), and Rauscher murine leukemia virus (RLV). No inhibition of the Sm-MTV enzyme activity was observed when treated with the latter three antisera with which the DNA polymerase activities of the corresponding retroviruses were fully inhibited. Only the antiserum against MPMV-enzyme, however, was found to slightly inhibit the Sm-MTV enzyme activity. These results indicate that Sm-MTV DNA polymerase has similar enzymological properties to those of MPMV and MuMTV and shares some common antigenic determinant group(s) with MPMV DNA polymerase.
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PMID:Biochemical and immunological characterization of Suncus murinus mammary tumor virus DNA polymerase. 241 16

Potential antiviral and antitumour nucleosides, 3'-fluoro-2', 3'-dideoxy-adenosine and -guanosine, have been synthesized by the chemical transglycosylation reaction using 5'-O-acetyl-3'-fluoro-2', 3'-dideoxy-thymidine and -uridine as donors of the carbohydrate fragment and persilylated 6-N-benzoyladenine and 2-N-palmitoylguanine as acceptors, respectively. 5'-Triphosphates of 3'-fluoro-2', 3'-dideoxy-thymidine, -cytidine, -adenosine, and -guanosine (dNTP(3'F] were synthesized and tested as terminators in cell-free system of DNA synthesis catalyzed by RNA-directed DNA polymerase (reverse transcriptase, RT) from the avian myeloblastosis virus (AMV) and E. coli DNA polymerase I (Klenow fragment). A method of estimating relative effectiveness of dNTP(3'F) incorporation into DNA growing chain in comparison with the natural substrates was developed. It is shown that, in case of AMV-RT, dATP(3'F), dCTP(3'F) incorporate 14 times less efficiently than dATP and dCTP respectively, and dTTP(3'F) 3 times less effectively than the corresponding natural substrates, whereas dGTP (3'F) is as efficient as dGTP. With E. coli DNA polymerase I (Klenow fragment) dATP (3'F) and dCTP(3'F) are ca. 100 times less efficient, and dTTP(3'F) and dGTP(3'F) are ca. 50 times less efficient than the respective natural substrates.
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PMID:[Synthesis of 2',3',-dideoxy-3'-fluoradenosine and -guanosine, their 5'-triphosphates and a study of 2',3'-dideoxy-3'-fluoronucleoside- 5'-triphosphates as substrates for DNA-polymerases]. 267 51

Ribonuclease-sensitive DNA synthesis is demonstrated in a cytoplasmic particulate fraction of normal human blood lymphocytes stimulated with phytohemagglutinin, but not in unstimulated lymphocytes. DNA polymerase purified from this fraction does not transcribe the heteropolymeric regions of 70S RNA from RNA tumor viruses, thus distinguishing this enzyme from the RNA-directed DNA polymerase (reverse transcriptase) found in oncogenic RNA viruses and human leukemic cells.
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PMID:Stimulated normal human lymphocytes contain a ribonuclease-sensitive DNA polymerase distinct from viral RNA-directed DNA polymerase. 411 71

A DNA polymerase purified from extracts of chick embryo catalyzes the synthesis of poly(dT) in the presence of poly(rA) or poly(dA) as template and poly(dT) or oligo(dT) as primer. Oligo- or polyribonucleotides are relatively ineffective initiators of polydeoxynucleotide polymerization. Using activated DNA as template, the enzyme catalyzes a repair-like reaction that resembles that catalyzed by RNA-directed DNA polymerase of RNA tumor viruses and Escherichia coli DNA polymerase II. With natural templates containing poly(rA) sequences, such as avian myeloblastosis virus RNA or rabbit globin mRNA, and oligo(dT) as initiator, principally poly(dT) is synthesized. Consequently, the enzyme differs from the RNA-directed DNA polymerase associated with RNA tumor viruses by its incapacity to transcribe heteropolymeric regions of RNA templates. The possible role of the enzyme in repair of DNA during transcription is discussed.
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PMID:Primer requirement and template specificity of a DNA polymerase of chick embryo. 412 33

Two DNA polymerase with properties of viral RNA-directed DNA polymerase can be found in RIII mouse milk. One enzyme is the polymerase of type-C viruses; this enzyme prefers manganese to magnesium with poly(rA).oligo(dT) as synthetic template, is inhibited by specific sera, and has an apparent molecular weight of 70,000. Milk from BALB/c and NIH Swiss mice contain a vast predominance of this type-C enzyme. The other DNA polymerase from RIII mouse milk prefers magnesium to manganese, is not inhibited by type-C antipolymerase serum, and appears larger on gel chromatography than the type-C viral polymerase. Its presence in milk from RIII mice and absence from milk of mice with low content of mammary tumor virus correlates to the relative degree of type-B virus expression in these mice. The DNA polymerase of Mason-Pfizer monkey virus, isolated from a rhesus monkey breast tumor, also has a marked preference for magnesium with poly(rA).oligo(dT), is not immunologically related to primate type-C viruses, and appears larger than the gibbon type-C enzyme on gel chromatography.
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PMID:Characterization and separation of viral DNA polymerase in mouse milk. 412 83

Antibodies against a large and a small DNA polymerase isolated from chicken embryos and against avian myeloblastosis virus DNA polymerase were used to study the serological relationships of the DNA polymerase activities of three avian systems with RNA and a DNA polymerase-avian leukosis-sarcoma viruses, reticuloendotheliosis viruses, and a fraction from uninfected chicken cells. The DNA polymerase activity of disrupted virions of all avian leukosis-sarcoma viruses tested was neutralized to the same extent by antibody against avian myeloblastosis virus DNA polymerase and was not neutralized by the antibodies against chicken cellular DNA polymerases. The viruses tested included induced leukosis viruses and Rous-associated virus-O. The DNA polymerase activity of disrupted virions of all of the reticuloendotheliosis viruses was not neutralized by any of the antibodies. The chicken endogenous RNA-directed DNA polymerase activity was neutralized partially or completely, in different experiments, by antibody against the small DNA polymerase isolated from chicken embryos, but was not neutralized by the other two antibodies.
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PMID:Lack of serological relationship among DNA polymerases of avian leukosis-sarcoma viruses, reticuloendotheliosis viruses, and chicken cells. 412 28

The relatedness of the RNAs of the three avian systems, including six avian leukosis-sarcoma viruses, four reticuloendotheliosis viruses, and the microsome fraction of normal uninfected chicken embryo cells, containing RNA and a DNA polymerase have been studied by nucleic acid hybridization. All six avian leukosis-sarcoma viruses have closely related nucleotide sequences; and all four reticuloendotheliosis viruses have closely related nucleotide sequences. But, almost no similarities were detected between the RNAs of avian leukosis-sarcoma viruses and reticuloendotheliosis viruses. The RNA template of the endogenous RNA-directed DNA polymerase activity of normal uninfected chicken cells had no detectable relationship to RNAs of avian leukosis-sarcoma and reticuloendotheliosis viruses.
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PMID:Lack of sequence homology among RNAs of avian leukosis-sarcoma viruses, reticuloendotheliosis viruses, and chicken endogenous RNA-directed DNA polymerase activity. 412 78


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