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)

The antibiotic tirandamycin (a 3-acyltetramic acid structurally related to streptolydigin) specifically inhibits transcription by interfering with the function of bacterial ribonucleic acid polymerase. Ribonucleic acid polymerases from rat liver nuclei are not subject to tirandamycin inhibition. Qualitatively, the mode of action of the antibiotic is identical to that of streptolydigin in inhibiting chain initiation as well as chain elongation during the transcriptional process. However, tirandamycin is approximately 40 times less potent than streptolydigin. The structures of the 3-acyl groups of the two acyltetramic acid antibiotics tirandamycin and streptolydigin differ only slightly in the degree of oxidation of the terminal dioxabicyclo (3.1)nonane system and possess the same stereochemistry (D. J. Duchamp, A. R. Branfman, A. C. Button, and K. L. Rinehart, 1973). More significantly, major differences occur at the 1 and 5 positions of the tetramic acids. Tirandamycin contains no substituents; streptolydigin contains a substituted acetamide function at position 5 and a sugar moiety at position 1. The lack of substituents at the 1 and 5 positions of the tetramic acid portion in tirandamycin is probably responsible for the reduced biopotency of tirandamycin as compared with streptolydigin.
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PMID:Tirandamycin, an inhibitor of bacterial ribonucleic acid polymerase. 79 Nov 8

Tirandamycin acts as a potent inhibitor of ribonucleic acid (RNA) polymerase in bacterial and mammalian cell-free test systems. The antibiotic inhibits the actively synthesizing template-enzyme-nascent RNA complex. Prolonged preincubation of RNA polymerase with tirandamycin prior to assay does not result in a drastic increase of tirandamycin inhibition. Tirandamycin inhibition is not reversed by further addition of deoxyribonucleic acid but is reversed upon further addition of RNA polymerase. Substantial inhibition of RNA polymerase is also obtained when the antibiotic is added at various times after initiation of the reaction. This suggests that tirandamycin interferes with the actively synthesizing template-RNA polymerase complex and inhibits chain elongation rather than chain initiation during RNA synthesis. Tirandamycin also interferes with oxidative phosphorylation in rat liver mitochondria and thus possesses two modes of action.
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PMID:Tirandamycin: inhibition of ribonucleic Acid polymerase. 1655 4

Tirandamycin inhibits respiration and phosphorylation in rat liver mitochondria. An investigation of individual reaction sequences occurring within the respiratory chain showed that the antibiotic stimulates reduced nicotinamide adenine dinucleotide (NADH)- and succinate-linked coenzyme Q reductase. NADH-linked reduction of tetrazolium salts remains unaffected by tirandamycin. Succinotetrazolium salt reductase is inhibited significantly. Reduction of cytochrome c by succinate is blocked by the antibiotic; NADH-cytochrome c reductase is inhibited but not completely blocked. Cytochrome c oxidase remains unaffected. Mitochondrial difference spectra prepared in the presence of tirandamycin indicate that the reduction of cytochrome b is not impaired but no reduction of cytochromes c or a is apparent. These results indicate that tirandamycin interferes with the respiratory chain at a point beyond the cytochrome b and prior to the cytochrome c reduction site. Tirandamycin acts also as a potent inhibitor of ribonucleic acid polymerase as discussed in the foregoing paper.
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PMID:Tirandamycin: inhibition of oxidative phosphorylation in rat liver mitochondria. 1655 5