Inhibition of peptide-chain initiation in Escherichia coli by hydroxylamine and effects on ribonucleic acid synthesis.
About: This article is published in Biochemistry.The article was published on 1970-11-10. It has received 19 citations till now. The article focuses on the topics: Hydroxylamine & Escherichia coli.
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TL;DR: This study will be concerned mainly with advances in the knowledge of the mode of action, selectivity, and specificity of inhibitors of protein synthesis over the last ten years.
400 citations
TL;DR: 280 Possible Involvement of fMet-tRNAF in the Regulation of RNA Synthesis........... 280 Peptide Chain Initiation Various Organisms................................... 281 Procaryotic cells.................................... 281 Eucaryotic Cells......................................................... 281 PEPTlDE CHAIN ELONGATION............................................ 281 Elongation Factors....................................................... 281 Process of Elongations........................................................ 282 Outline of the steps in elongation
151 citations
TL;DR: The results indicate that the synthesis ofppGpp is independent of RNA synthesis, but suggest that a coupling exists between ppGpp formation and an idling reaction of one of the initiation steps of protein synthesis.
Abstract: In rel+ strains of Escherichia coli guanosine 2′(3′)-diphosphate-5′-diphosphate (ppGpp) was found to accumulate (a) during amino acid starvation of an auxotrophic strain, (b) during heating to the non-permissive temperature of a valSts strain, (c) during heating of a wild-type strain to temperatures above 46°C and (d) during treatment with trimethoprim or hydroxylamine. A rapid decay of the accumulated ppGpp was observed after addition of chloramphenicol, tetracycline, fusidic acid, erythromycin, puromycin or colicin E3 to susceptible cultures. All of these antibiotics give a rapid and complete inhibition of protein synthesis. Streptomycin showed a delayed inhibitory action on protein synthesis and had little effect on the level of accumulated ppGpp. The addition of rifampicin also results in a delayed decay of ppGpp.
These results indicate that the synthesis of ppGpp is independent of RNA synthesis, but suggest that a coupling exists between ppGpp formation and an idling reaction of one of the initiation steps of protein synthesis.
119 citations
TL;DR: The inhibitory effect on aminoacyl‐tRNA synthetases and the antiproliferative action on P388D1 or P388 could not be correlated and Micromolar concentrations of the compounds S‐tritylcysteine, fenitropan and ß‐chloroalanine gave strong growth inhibition.
Abstract: Amino acid antagonists with proven or potentially inhibitory activities on aminoacyl-tRNA synthetases were tested for their antiproliferative effect against Escherichia coli B. The compds. 4- and 6-fluorotryptophan, 5-methyltryptophan, selenocysteine, and beta -(2-thienyl)alanine gave strong growth inhibition in minimal medium, which disappeared after the addn. of structurally related natural amino acids or in an enriched broth. The inhibitory effect on aminoacyl-tRNA synthetases and the minimal inhibitory concn. for growth inhibition in minimal medium could not be correlated.
57 citations
TL;DR: The most important antibiotics acting at the translational level are integrated into this network of data and the binding sites and the inhibition mechanisms of the drugs, together with the ribosomal components altered in resistant mutants are described.
Abstract: Most of the known antibiotics act at the level of protein biosynthesis probably due to the extraordinary complexity of the translational machinery which can be interfered with at many points. At first a survey is given of our present knowledge covering the structure and function of the prokaryotic ribosome. The most important antibiotics acting at the translational level are integrated into this network of data. The binding sites and the inhibition mechanisms of the drugs, together with the ribosomal components altered in resistant mutants are described. Finally, the points of interference with the translational machinery are indicated in an extended scheme of ribosomal functions.
50 citations
References
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TL;DR: A rapid and sensitive method has been described for the measurement of amino acid incorporation in cell-free systems and has been applied to both C14- and H3-labeled proteins.
2,068 citations
TL;DR: The N10-formyltetrahydrofolate:methionyl soluble ribonucleic acid transformylase has been purified over 1500-fold from Escherichia coli B and although not homogeneous at this stage, the enzyme was of sufficient purity to determine some physical characteristics.
117 citations
114 citations
TL;DR: The shortcomings and limitations of the techniques most frequently is used in studying the regulation of macromolecule synthesis and pointed out the need for a different approach to this study is discussed in this chapter.
Abstract: Publisher Summary The chapter discusses the regulation of RNA synthesis in bacteria. The regulation of RNA synthesis in bacterial cells has been explained in this chapter. Formation of these macromolecules seems to be geared in a precise and unique manner to the over-all protein-synthesizing potential of a cell in its particular environment. The synthesis of ribosomal ribonucleic acid (rRNA) is a variable fraction of a cells total biosynthetic activity, depending on the growth rate, so that the concentration of rRNA in a cell is a simple linear function of the over-all rate of protein synthesis during steady state growth. The conclusion that the constancy of the rate of protein synthesis calculated per unit of rRNA is the prime physiological function of this integration. The regulation seems to be achieved, by a reversible inhibition of the RNA-forming machinery of the cell, and most of the available evidence is consistent, with a model, in which amino acids reverse this inhibition, perhaps by combining with their respective sRNA. The shortcomings and limitations of the techniques most frequently is used in studying the regulation of macromolecule synthesis and pointed out the need for a different approach to this study is discussed in this chapter. The method shows promise of becoming an important tool for analyzing cellular regulatory devices.
90 citations
TL;DR: The growth of Escherichia coli cells in rich, thymine-containing medium was stopped by the addition of trimethoprim, an inhibitor of dihydrofolate reductase, and hydroxylamine inhibited the amino acid incorporation directed by f2 bacteriophage RNA.
Abstract: The growth of Escherichia coli cells in rich, thymine-containing medium was stopped by the addition of trimethoprim, an inhibitor of dihydrofolate reductase. In an extract of these cells (supernatant from an extract centrifuged at 30,000g) amino acid incorporation at 0.005M magnesium-ion concentration, directed by f2 bacteriophage RNA depended strictly on added formylmethionyl-transfer RNA or N5-formyltetrahydrofolate. Hydroxylamine inhibited the amino acid incorporation directed by f2 bacteriophage RNA, when N5-formyltetrahydrofolate had been added, but had no effect when formylmethionyl transfer RNA had been added.
88 citations