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 mode of action of the antibiotic pseudomonic acid has been studied in Escherichia coli. Pseudomonic acid strongly inhibits protein and RNA synthesis in vivo. The antibiotic had no effect on highly purified DNA-dependent RNA polymerase and showed only a weak inhibitory effect on a poly(U)-directed polyphenylalanine-forming ribosomal preparation. Chloramphenicol reversed inhibition of RNA synthesis in vivo. Pseudomonic acid had little effect on RNA synthesis in a regulatory mutant, E. coli B AS19 RC(rel), whereas protein synthesis was strongly inhibited. In pseudomonic acid-treated cells, increased concentrations of ppGpp, pppGpp and ATP were observed, but the GTP pool size decreased, suggesting that inhibition of RNA synthesis is a consequence of the stringent control mechanism imposed by pseudomonic acid-induced deprivation of an amino acid. Of the 20 common amino acids, only isoleucine reversed the inhibitory effect in vivo. The antibiotic was found to be a powerful inhibitor of isoleucyl-tRNA synthetase both in vivo and in vitro. Of seven other tRNA synthetases assayed, only a weak inhibitory effect on phenylalanyl-tRNA synthetase was observed; this presumably accounted for the weak effect on polyphenylalanine formation in a ribosomal preparation. Pseudomonic acid also significantly de-repressed threonine deaminase and transaminase B activity, but not dihydroxyacid dehydratase (isoleucine-biosynthetic enzymes) by decreasing the supply of aminoacylated tRNA(Ile). Pseudomonic acid is the second naturally occurring inhibitor of bacterial isoleucyl-tRNA synthetase to be discovered, furanomycin being the first.
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PMID:Inhibition of isoleucyl-transfer ribonucleic acid synthetase in Escherichia coli by pseudomonic acid. 36 75

The synthesis of ilv-specific messenger ribonucleic acid (mRNA) by extracts of Escherichia coli K-12 has been demonstrated in a deoxyribonucleic acid (DNA)-dependent, coupled transcription-translation system. ilv-Specific mRNA was determined by hybridization either to double-stranded lambdacI857St68h80dilv DNA (lambdah80dilv DNA) immobilized on nitrocellulose filters or to its separate l and r strands in liquid. During conditions optimal for protein synthesis, slightly more than 6% of the total [(3)H]RNA synthesized by S-30 extracts of the threonine deaminase-negative strain CU5136 was ilv-specific. Of this RNA, nearly 30% was complementary to the l (correct) strand. Total ilv-specific mRNA synthesis in vitro was not affected by omission of valine or all 20 amino acids from the reaction mixture. Hybridization of ilv-specific mRNA made in vitro to the l strand of lambdah80dilv DNA was effectively reduced in the presence of unlabeled RNA extracted from an ilv derepressed strain but not from an ilv deletion strain. In a purified transcription system, employing commercial RNA polymerase, twofold more ilv-specific mRNA was synthesized than in the coupled system, but this increase was entirely due to greater transcription of the r (incorrect) strand. An S-30 extract prepared from a strain isogenic to strain CU5136 but derepressed for ilvA gene expression synthesized twofold more ilv-specific mRNA in the coupled system. The significance of these findings is discussed.
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PMID:Deoxyribonucleic acid-directed in vitro synthesis of ilv-specific messenger ribonucleic acid by extracts of Escherichia coli K-12. 461 11

The production by Neurospora of the enzymes of isoleucine and valine synthesis in response to specific end product-derived signals depends upon the presence of an effective leu-3 regulatory product and its effector alpha-isopropylmalate (alpha-IPM). In leu-3(+) strains, threonine deaminase production is repressed as a function of available isoleucine, acetohydroxy acid synthetase as a function of valine, and the isomeroreductase and dihydroxy acid dehydratase as a function of isoleucine and leucine. In the absence of an effective leu-3 regulatory product, alpha-isopropylmalate, or both, the production of isoleucine and valine biosynthetic enzymes is fixed at or near fully repressed levels even under conditions of severe end product limitation. Thus, in addition to its involvement in the regulation of expression of the three structural genes of leucine synthesis, the leu-3 alpha-IPM regulatory product is necessary for full expression of at least four genes specifying the structure of the enzymes of isoleucine and valine synthesis. It is suggested that the leu-3 alpha-IPM regulatory element may facilitate transcription of the genetically dispersed cistrons either by imposing specificity on ribonucleic acid polymerase for structurally similar promoters adjacent to each of the cistrons or by "opening" promoters after interaction with nearly identical stretches of deoxyribonucleic acid near each of the structural genes.
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PMID:Role of the leu-3 cistron in the regulation of the synthesis of isoleucine and valine biosynthetic enzymes of Neurospora. 482 4

The threonine dehydratase IlvA is part of the isoleucine biosynthesis pathway in the Gram-positive model bacterium Bacillus subtilis. Consequently, deletion of ilvA causes isoleucine auxotrophy. It has been reported that ilvA pseudo-revertants having a derepressed hom-thrCB operon appear in the presence of threonine. Here we have characterized two classes of ilvA pseudo-revertants. In the first class the hom-thrCB operon was derepressed unmasking the threonine dehydratase activity of the threonine synthase ThrC. In the second class of mutants, threonine biosynthesis was more broadly affected. The first class of ilvA pseudo-revertants had a mutation in the Phom promoter (P*hom ), resulting in constitutive expression of the hom-thrCB operon. In the second class of ilvA pseudo-revertants, the thrR gene encoding a putative DNA-binding protein was inactivated, also resulting in constitutive expression of the hom-thrCB operon. Here we demonstrate that ThrR is indeed a DNA-binding transcription factor that regulates the hom-thrCB operon and the thrD aspartokinase gene. DNA binding assays uncovered the DNA-binding site of ThrR and revealed that the repressor competes with the RNA polymerase for DNA binding. This study also revealed that ThrR orthologs are ubiquitous in genomes from the Gram-positive phylum Firmicutes and in some Gram-negative bacteria.
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PMID:ThrR, a DNA-binding transcription factor involved in controlling threonine biosynthesis in Bacillus subtilis. 2726 Jun 60