The Effects of Streptomycin or Dihydrostreptomycin Binding to 16S RNA or to 30S Ribosomal Subunits

Garvin, Robert T.; Biswas, Debajit K.; Gorini, Luigi

doi:10.1073/pnas.71.10.3814

Cited by 44 publications

(28 citation statements)

References 15 publications

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“…However, although they are virtually equipotent as regards killing and inhibition of cell-free protein synthesis, streptomycin has a much higher affinity for the bacterial ribosome than dihydrostreptomycin. This result confirms the observation of Garvin et al [5].…”

Section: Discussionsupporting

confidence: 83%

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Paromomycin and Dihydrostreptomycin Binding to Escherichia coli Ribosomes

Lando¹,

Cousin²,

Ojasoo³

et al. 1976

European Journal of Biochemistry

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Paromomycin binds specifically to a single type of binding site on the 70‐S streptomycin‐sensitive Escherichia coli ribosome. This site is different from that of dihydrostreptomycin since paromomycin binds to streptomycin‐resistant ribosomes and since dihydrostreptomycin does not compete for paromomycin binding. Paromomycin binding, unlike dihydrostreptomycin binding, is independent of changes in ribosome concentration but influenced by magnesium ion concentration. Moreover, paromomycin does not bind to the 30‐S subunit of the streptomycin‐sensitive ribosome, except in the presence of dihydrostreptomycin, which probably induces the conformational changes necessary for a paromomycin binding site. This induction does not occur with streptomycin‐resistant ribosomes. Neither antibiotic binds to the 50‐S subunit. In general, binding of the one antibiotic increases the number of sites available for binding of the other. Both antibiotics hibit marked non‐specific binding at high antibiotic/ribosome ratios. Competition studies have enabled the classification of other aminoglycosides according to their ability to compete for the paromomycin and dihydrostreptomycin binding sites. Derivatives structurally related to paromomycin compete for its binding, the degree of competition being related to antibacterial activity, but do not compete for dihydrostreptomycin binding; they, on the contrary, increase the number of dihydrostreptomycin binding sites. Neither gentamicin nor kanamycin derivatives, which induce a high level of misreading, nor kasugamycin and spectinomycin, which do not induce misreading, compete for paromomycin or dihydrostreptomycin binding sites. Other sites may be involved in the binding of these aminoglycosides and in inducing misreading.

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Section: Discussionsupporting

confidence: 83%

“…It is still a matter of controversy whether protein S12, responsible for ribosome sensitivity to these antibiotics, is an integral part of the binding site. Moreover, labelled streptomycin and, to a very much less extent, labelled dihydrostreptomycin, bind to 16-S RNA from 30-S ribosomal subunits [5].…”

mentioning

confidence: 99%

Paromomycin and Dihydrostreptomycin Binding to Escherichia coli Ribosomes

Lando¹,

Cousin²,

Ojasoo³

et al. 1976

European Journal of Biochemistry

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“…12 A resistência à SM em M. tuberculosis ocorre por mutações no alvo do fármaco, mais especificamente nos ribossomos. O principal sítio de mutação é o gene rpsL, que codifica a proteína ribossomal S12, 5,11,15,33 em que ocorrem mutações resultando na substituição de um único aminoácido.…”

Section: Resistência à Estreptomicinaunclassified

Tuberculose resistente: revisão molecular

et al. 2002

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ResumoO progresso na compreensão dos mecanismos de resistência aos fármacos usados no tratamento da tuberculose tem permitido o desenvolvimento de novos métodos para a detecção da tuberculose resistente. A resistente aos fármacos representa uma ameaça para os programas de controle da tuberculose. Para tanto, é necessário conhecer o padrão de sensibilidade das linhagens para fornecer o tratamento adequado. Os estudos moleculares dos mecanismos de ação dos fármacos antituberculose têm elucidado as bases genéticas da resistência aos fármacos em Mycobacterium tuberculosis. Os mecanismos de resistência aos fármacos na tuberculose são causados por mutações cromossomais em diferentes genes da bactéria. Durante a exposição aos fármacos, há uma pressão seletiva favorecendo o desenvolvimento de linhagens resistentes. A tuberculose multirresistente é um problema nacional e internacional que traz sérias dificuldades para o controle global da doença. Realizou-se uma revisão sobre os mecanismos moleculares associados à resistência aos fármacos com ênfase nas novas perspectivas para detectar os isolados resistentes. AbstractProgress to understanding the basis of resistance to antituberculous drugs has allowed molecular tests for detection of drug-resistant tuberculosis to be developed. Drug-resistant tuberculosis poses a threat to tuberculosis control programs. It is necessary thus to know drug susceptibilities of individual patient's strain to provide the appropriate drug combinations. Molecular studies on the mechanism of action of antituberculous drugs have elucidated the genetic basis of drug resistance in M. tuberculosis. The mechanisms of drug resistance in tuberculosis are a result of chromosomal mutations in different genes of the bacteria. Upon drug exposure there is a selective pressure for such resistant mutants. Multidrug-resistant tuberculosis is a health problem of increasing significance for the whole global community. This paper reviews the molecular mechanisms associated with drugresistance as well the new perspectives for detecting resistant isolates. Current Comments Atualização

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“…LELONG et al 19) have investigated the binding site of streptomycin, using specific antibody fragments (Fab) for 30S ribosomal proteins, and observed that antibodies for S1, S10, S11, S18, S19, S20 and S21 interfere with the binding of dihydrostreptomycin to 30S or 70S ribosomes. BISWAS and GORINI20) , and GARVIN et al 21) have presented evidence that 16S RNA is the binding site of streptomycin and that it binds 2 molecules per RNA molecule. As described above, the diverse results obtained by a number of investigators using different methods make it impossible to specify any ribosomal component(s) for the attachment site of streptomycin.…”

Section: Discussionmentioning

confidence: 99%

Ribosomal proteins S9 and L6 participate in the binding of(3H)dibekacin to E. coli ribosomes.

Akiyama

Tanaka

1981

J. Antibiot.

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The degrees of binding of [3H]dibekacin to LiCl-treated cores of E. coli ribosomes were reduced by increasing LiCl concentrations. The 1.15 M LiCl core lost 70~80% of the original binding capacity. The antibiotic attachment to the 1.15 M LiCl core was restored by reconstitution with the split proteins (SP), which were obtained by the treatment of 70S ribosomes with LiCl at concentrations of 0.8-1.15 M. The basic proteins, split off during the transition from 0.4 M LiCl core to 0.8 ~ 1.15 M LiCl core, seemed to be involved in the drug binding. SP0.4~1.15, which was obtained by the treatment of the 0.4 M LiCl core with 1.15 M LiCl, was fractionated by CM-Sephadex C-25 column chromatography, and each fraction was assayed for protein composition and the capability of restoring the ability of the 1.15 M LiCl core to bind the drug. Of ribosomal proteins eliminated with 1.15 M LiCl, the addition of either S9 or L6 alone to the 1.15 M LiCl core was observed to restore approximately 50% of the binding as compared to the 70S ribosome alone, and both proteins restored about 70% of the binding. The results suggested that ribosomal proteins S9 and L6 were involved in the attachment of [3H]dibekacin to the ribosome. The antibiotic binding to the 70S ribosome and 1.15 M LiCl core reconstituted with S9 or L6 was considerably inhibited by unlabelled dibekacin or kanamycin, and partially inhibited by gentamicin or neomycin, but was not significantly affected by streptomycin or viomycin.The mechanism of action of the aminoglycoside group of antibiotics differ. Kasugamycin binds to the 30S ribosomal subunit and selectively inhibits initiation of protein synthesis1,2). Codon misreading is caused by streptomycin, kanamycin, neomycin, gentamicin and related aminoglycosides, but not by kasugamycin3). Translocation of peptidyl-tRNA from the acceptor site to the donor site on the ribosome is blocked by kanamycin, neomycin, gentamicin and related antibiotics but not significantly by streptomycin4). Kanamycin interferes with the translocation by fixing peptidyl-tRNA to the acceptor site but not to the donor site5). Streptomycin selectively binds to the 30S ribosomal subunit (cf. a review by WALLACE et al.6)); but kanamycin, neomycin and gentamicin bind to both 30S and 50S ribosomal subunits4). In some kanamycin-resistant mutants, the resistance is attributed to mutational alterations of the 30S ribosomal subunit in some mutants, and to the 50S subunit in the others7), but streptomycin resistance is due exclusively to changes of the 30S subunit6).For the purpose of elucidating what kind of ribosomal proteins are involved in the binding of kanamycin to the ribosome, we have studied the binding of [3H]dibekacin to the reconstituted ribosomes, following the method of SCHREINER and NIERHAUS8), and the results are presented in this publication.[3H]Dibekacin is employed in the current experiment, because the highly radioactive compound is available. Materials and Methods[3',4 -3H]Dibekacin (66 yCi/mg) was kindly supplied by Dr. S. FUKATSU, Centra...

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The Effects of Streptomycin or Dihydrostreptomycin Binding to 16S RNA or to 30S Ribosomal Subunits

Cited by 44 publications

References 15 publications

Paromomycin and Dihydrostreptomycin Binding to Escherichia coli Ribosomes

Paromomycin and Dihydrostreptomycin Binding to Escherichia coli Ribosomes

Tuberculose resistente: revisão molecular

Ribosomal proteins S9 and L6 participate in the binding of(3H)dibekacin to E. coli ribosomes.

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