Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase (EC 2.7.7.6) isolated from a rifampin-sensitive strain of Mycobacterium smegmatis was 90% inhibited by 1 mug of rifampin per ml; enzyme from a rifampin-resistant mutant was not affected by this concentration of antibiotic. Inhibition of phenylalanine-1-(14)C incorporation by rifampin in growing cultures was complete about 6 min after addition of antibiotic. Under the same conditions, uracil-2-(14)c incorporated was blocked after 1.5 to 2 min. Rifampin kills M. smegmatis very slowly. When rifampin-inhibited cultures were transferred to a rifampin-free medium, there was a partial resumption of uracil-2-(14)C incorporation, even in the presence of chloramphenicol. We conclude that a primary event in the inhibition of M. smegmatis by rifampin is the block of DNA-dependent RNA polymerase.
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PMID:Mechanism of action of rifampin on Mycobacterium smegmatis. 494 61

A Bacillus subtilis mutant, that was selected for rifampin resistance produces spores with an altered morphology. The mutant spores are pleomorphic and differ both in shape and size from the wild-type spores. They frequently have an exosporium that is usually absent from wild-type spores. The mutant spores are similar to the wild-type spores in heat resistance, dipicolinic acid content, and density, but exhibit a slower rate of germination, outgrowth, and growth. In vitro studies show that the RNA polymerase of the mutant is resistant to rifampin inhibition, whereas the wild-type enzyme is completely inhibited by low concentrations of the antibiotic. Rifampin resistance and the altered spore morphology are contransformed with 100% frequency, suggesting that the altered morphology is caused by an alteration in the RNA polymerase.
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PMID:Bacillus subtilis mutant altered in spore morphology and in RNA polymerase activity. 498 21

1. The two subunits alpha and beta of Halobacterium cutirubrum DNA-dependent RNA polymerase are required in equimolar amounts for RNA synthesis to occur in vitro at the maximum rate. 2. In the absence of bivalent cations no interaction occurs between alpha and beta subunits or between the subunits and DNA. 3. Mn(2+) causes the subunits to form a 1:1 complex that still does not bind to the template. 4. Mg(2+) permits binding of the Mn(2+)-mediated complex to DNA. 5. The complete enzyme, alphabeta, is inhibited by rifampicin and only the beta subunit relieves the inhibition when added in excess. 6. Rifampicin-insensitive, template-dependent RNA synthesis occurs in the presence of protein alpha alone provided an oligonucleotide with a 5'-purine terminus is supplied as primer. 7. In the primed reaction with the alpha protein and an oligonucleotide, the template specificity is independent of the ionic strength, in contrast with the marked effect of salt concentration on the template specificity of the complete enzyme. 8. It is concluded that the beta protein controls the specificity of chain initiation and the template specificity of the complete enzyme and also carries the rifampicin-binding site, whereas the catalytic site is on the alpha subunit.
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PMID:The role of Halobacterium cutirubrum deoxyribonucleic acid-dependent ribonucleic acid polymerase subunits in initiation and polymerization. 507 56

Adenosine, TMP, ADP, ATP and UpA along with guanosine and tis analogous derivatives have different reactivity towards [alpha-32P]UTP in abortive initiation reactions catalyzed by E. coli RNA polymerase on T2 DNA in the presence of Mg2+ or Mn2+. Rifampicin moderately inhibited almost all of the above mentioned reactions, except the ATP and the GTP which were even 2.5 times more reactive in the presence of this antibiotic.
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PMID:[Participation of various adenosine and guanosine derivatives in the abortive RNA synthesis initiation reaction: effect of Mg2+, Mn2+, and rifampicin]. 616 Mar 85

Although the antibiotic rifampicin inhibits the transcription of poly[d(A-T)] by E.coli RNA polymerase, a series of short oligonucleotides is produced. It is claimed that the overall inhibition of RNA synthesis by rifampicin is caused by a destabilising effect on the binding of the intermediate oligonucleotides to the active enzyme-DNA complex. Rifampicin itself can only interact specifically with RNA polymerase if the enzyme is free or in a binary complex with DNA. However, the enzyme is not susceptible in a ternary complex, even if the "RNA" is as short as a trinucleotide.
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PMID:Rifampicin inhibition of RNA synthesis by destabilisation of DNA-RNA polymerase-oligonucleotide-complexes. 617 47

Using the plasmid pNF1337 as template, a mRNA preparation has been obtained that directs the in vitro synthesis of fMet-Val, the N-terminal dipeptide of the beta subunit of RNA polymerase. RNA polymerase holoenzyme specifically inhibits the mRNA-directed synthesis of fMet-Val showing that the autoregulation by RNA polymerase of beta, beta 1 synthesis is at the level of translation. L factor (nusA gene product) stimulates the synthesis of fMet-Val from a DNA template but not from mRNA. Rifampicin has no effect on the mRNA-directed synthesis of fMet-Val or the ability of RNA polymerase to inhibit fMet-Val synthesis.
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PMID:Translational control of the expression of the beta subunit gene of E. coli RNA polymerase. 630 1

Rifampin specifically inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription, by forming a stable drug-enzyme complex with a binding constant of 10(-9) M at 37 C. The corresponding mammalian enzymes are not affected by rifampin. Bacterial resistance to rifampin is caused by mutations leading to a change in the structure of the beta subunit of RNA polymerase. Such resistance is not an all-or-nothing phenomenon; rather, a large number of RNA polymerases with various degrees of sensitivity to rifampin have been found. No strict correlation exists between enzyme sensitivity and MIC values, since inhibition of RNA synthesis does not always show up to the same extent in the two different test systems used for the determination of these values.
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PMID:Rifampin: mechanisms of action and resistance. 635 75

The rate of adaptation of Escherichia coli K-12 NF930 spoT1 cells with elevated intracellular level of ppGpp to various minimal media was studied. It has been found that the rate of adaptation of spoT cells, like that of parent and rel strains, depends mainly on the rate of derepression of the ilv operon. The maximal rate of the ilv operon derepression was observed when an optimal concentration of ppGpp was maintained in cells. Derepression of the ilv operon is sharply delayed when the level of ppGpp is elevated or reduced. Mutations altering the translation system do not change the rate of adaptation of spoT cells. Rifampicin resistance mutations which altered the structure of RNA polymerase change the rate of adaptation of spoT cells to minimal media, especially to those containing serine at high concentrations. The possible role of serine in the regulation of ppGpp degradation system is discussed.
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PMID:[Expression of the amino acid operons in Escherichia coli strains with an altered transcription and translation apparatus. IV. The effect of mutations disturbing the coupling of the transcription and translation processes on ilv-operon expression in cells carrying the mutation in the spoT gene]. 635 48

The genes for the beta and beta' subunits of RNA polymerase, rpoB and rpoC, and the genes for the two ribosomal proteins, rplL and rplJ, are part of the beta operon. Although this operon and contains a single strong promoter, the genes of the operon are not always coordinately expressed in vivo. This has now been confirmed in vitro where the lack of coordinate expression has been shown to be correlated with the selective inhibition of rpoB and rpoC gene expression by RNa polymerase. Rifampicin, which stops the initiation of transcription, also relieves this autogenous inhibition of beta and beta' (beta beta') synthesis. The inhibitory action of RNA polymerase and its reversal by rifampicin most likely occurs at a posttranscriptional or translation level.
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PMID:Negative regulation of beta and beta' synthesis by RNA polymerase. 646 Sep 12

The results of recent experiences with experimental tuberculous chemotherapy in the mouse give information on the activity of rifampicin (RMP) administered intermittently and on the activity of Cyclopentyl-Rifampicin (or DL473). The activity of RMP decreases as one spaces the treatment without increasing the dose. These observations are compatible with the known facts concerning the mechanism of action of RMP on RNA polymerase, and are unfavourable as regards the intermittent administration of RMP. Cyclopentyl-Rifampicin, a new derivative of Rifamycine SV, administered once per week, is as active as RMP administered six days per week, both in the initial as well as the continuation phase of treatment.
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PMID:[Activity of intermittently administered rifampicin and cyclopentyl rifamycin (or DL473) on experimental tuberculosis in the mouse]. 666 98


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