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)

Procedures were established for the isolation and partial purification of DNA polymerase, RNA polymerase and poly(A) polymerase activities from the cytoplasm and nuclei of NIH-Swiss mouse embryos. Based on the elution pattern of these enzyme activities from DEAE-cellulose and phosphocellulose columns in Tris-HCl buffer, pH 8.0, the apparent basicities of the enzymes can be arranged as follows: cytoplasmic(C) poly(A) polymerase greater than (C)DNA polymerase beta greater than (C)DNA polymerase alpha and nuclear(N) poly(A) polymerase greater than (N)DNA polymerase greater than (N)RNA polymerase I greater than (N)RNA polymerase II. Twenty rifamycins, including rifamycin B, rifamycin S, rifamycin SV, and rifamycin SV derivatives, were examined for their ability to inhibit the above mentioned nucleic acid polymerizing enzymes and Simian sarcoma virus type I (SSV-1) reverse transcriptase. Rifamycin SV 3'-formyldiphenylhydrazone, rifamycin SV 3'-formyl-n-octyloxime (AF/013) and rifamycin SV 3'-formyldiphenylmethyloxime (AF/05) inhibited all the tested enzyme activities. Rifamycin SV 3'-formylpropylphenyloxime (AF/015) inhibited cellular nucleic acid polymerase activities but not SSV-1 DNA polymerase activity. Rifamycin SV 3'-formyldinitrophenylhydrazone (AF/DNFL) strongly inhibited reverse transcriptase activity but did not inhibit cellular DNA polymerase activities. AF/DNFI slightly inhibited RNA and poly(A) polymerase activities. Rifamycin SV 3'-formyldipropylhydrazone (AF/DPI) and 2,6-dimethyl-4-N-benzyldemethyl-rifampicin (AF/ABDMP) slightly inhibited reverse transcriptase activity but did not inhibit cellular nucleic acid polymerase activities. Active rifamycin derivatives inhibited enzyme reactions by interacting with the enzyme proteins. Nascent polynucleotide chain elongation continued although at a reduced rate in the presence of inhibitor. The addition of increasing concentrations of nonionic detergent (Triton X-100) to rifamycin-inhibited enzyme reactions fully restored enzyme activities. The presence of highly lipophilic 3'-side chains on active rifamycins and the reversibility of enzyme inhibition by Triton X-100 suggest that the tested nucleic acid polymerizing enzymes may have hydrophobic regions with which inhibitory rifamycins interact.
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PMID:Interaction of rifamycins with mammalian nucleic acid polymerizing enzymes. 6 93

Rifamycin antibiotics, which inhibit RNA-directed DNA polymerase of Rauscher leuckemia virus, prevent the leukemogenic activity of the virus, and the effect of leukemogenesis correlates with the magnitude of inhibition of the purified enzyme. This inhibition of enzyme activity by rifamycin SV derivatives is due to a relatively tight binding between the enzymes and the inhibitors, yet the binding can be reversed by nonionic detergent. The results of this study suggest that RNA-directed DNA polymerase is essential for induction of leukemia by exogenous virus and correlate with the previous observation that the same derivatives block viral transformation in vitro.
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PMID:RNA-directed DNA polymerase and virus-induced leukemia in mice. 412 70

Specific inhibitors and anti-DNA polymerase alpha IgG have been utilized to probe for similarities between cytoplasmic rat hepatic glucocorticoid receptors and DNA polymerase alpha [DNA nucleotidyltransferase (DNA-directed), EC 2.7.7.7]. Rifamycin AF/013, an inhibitor of RNA and DNA polymerase activities, significantly inhibited the binding of activated [6,7-3H]-triamcinolone acetonide (TA) receptor complexes to DNA-cellulose. beta-Lapachone, an inhibitor of DNA polymerase alpha and reverse transcriptase activities, inhibited the specific binding of [6,7-3H]TA when preincubated with unbound receptors. Aphidicolin, another DNA polymerase alpha inhibitor, failed to inhibit any of the glucocorticoid-receptor functions tested. Two specific anti-DNA polymerase alpha IgGs interfered with glucocorticoid receptor functions as measured by their ability to inhibit the binding of [6,7-3H]TA to unbound receptors (85% maximal inhibition) and, to a lesser extent, to inhibit the binding of activated [6,7-3H]TA receptor complexes to DNA-cellulose (50% maximal inhibition). The anti-DNA polymerase alpha IgG and beta-lapachone failed to affect the binding of tritiated estradiol, progesterone, or 5 alpha-dihydrotestosterone to their receptors in appropriate rat target tissues or the binding of [1,2-3H]hydrocortisone to serum transcortin. The most obvious interpretation of these data is that cytoplasmic glucocorticoid receptors and DNA polymerase alpha share antigenic determinants. An alternative interpretation is that the polyclonal anti-DNA polymerase alpha antibody contains IgG molecules raised against calf thymus cytoplasmic activated glucocorticoid-receptor complexes that copurified with DNA polymerase alpha used as the antigen. Taken collectively, however, the antibody and inhibitor data suggest a relationship between DNA polymerase alpha and the glucocorticoid receptor.
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PMID:Correlations between the activities of DNA polymerase alpha and the glucocorticoid receptor. 681 51

Rifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to beta-subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been discovered that are effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessibility of recombinant DNA techniques to increase rifamycin production are reviewed.
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PMID:Recent trends in rifamycin research. 751 53

HIV and tuberculosis (TB) are leading global causes of mortality and morbidity, and yet effective treatment exists for both conditions. Rifamycin-based antituberculosis therapy can cure HIV-related TB and, where available, the introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of AIDS and death. Optimal treatment regimens for HIV/TB co-infection are not yet clearly defined. Combinations are limited by alterations in the activity of the hepatic cytochrome P450 (CYP) enzyme system, which in particular may produce subtherapeutic plasma concentrations of antiretroviral drugs. For example, protease inhibitors often must be avoided if the potent CYP inducer rifampicin is co-administered. However, an alternative rifamycin, rifabutin, which has similar efficacy to rifampicin, can be used with appropriate dose reduction. Available clinical data suggest that, for the majority of individuals, rifampicin-based regimens can be successfully combined with the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Most available HAART regimens in areas that have a high burden of TB contain one or the other of these drugs as a backbone. However, significant questions remain as to the optimal dose of either agent required to ensure therapeutic plasma concentrations, especially in relation to particular ethnic groups. The timing of HAART initiation after starting antituberculosis therapy continues to be controversial. Debate centres upon whether early initiation of HAART increases the risk of paradoxical reactions (immune reconstitution-related events) and other adverse events, or whether delay greatly elevates the risk of disease progression. Further prospective clinical data are needed to help inform practice in this area.
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PMID:Tuberculosis and HIV co-infection: a practical therapeutic approach. 1718 73