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. 1991 Oct;10(10):3099–3103. doi: 10.1002/j.1460-2075.1991.tb07863.x

Interaction of antibiotics with A- and P-site-specific bases in 16S ribosomal RNA.

J Woodcock 1, D Moazed 1, M Cannon 1, J Davies 1, H F Noller 1
PMCID: PMC453027  PMID: 1915283

Abstract

We have studied the interactions of the antibiotics apramycin, kasugamycin, myomycin, neamine and pactamycin with 16S rRNA by chemical probing of drug-ribosome complexes. Kasugamycin and pactamycin, which are believed to affect translational initiation, protect bases in common with P-site-bound tRNA. While kasugamycin protects A794 and G926, and causes enhanced reactivity of C795, pactamycin protects G693 and C795. All four of these bases were previously shown to be protected by P-site tRNA or by edeine, another P-site inhibitor. Apramycin and neamine, which both induce miscoding and inhibit translocation, protect A1408, G1419 and G1494, as was also found earlier for neomycin, gentamicin, kanamycin and paromomycin. A1408 and G1494 were previously shown to be protected by A-site tRNA. Surprisingly, myomycin fails to give strong protection of any bases in 16S rRNA, in spite of having an apparently identical target site and mode of action to streptomycin, which protects several bases in the 915 region. Instead, myomycin gives only weak protection of A1408. These results suggest that the binding site(s) of streptomycin and myomycin have yet to be identified.

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Selected References

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  1. Allen P. N., Noller H. F. Mutations in ribosomal proteins S4 and S12 influence the higher order structure of 16 S ribosomal RNA. J Mol Biol. 1989 Aug 5;208(3):457–468. doi: 10.1016/0022-2836(89)90509-3. [DOI] [PubMed] [Google Scholar]
  2. Atmadja J., Stiege W., Zobawa M., Greuer B., Osswald M., Brimacombe R. The tertiary folding of Escherichia coli 16S RNA, as studied by in situ intra-RNA cross-linking of 30S ribosomal subunits with bis-(2-chloroethyl)-methylamine. Nucleic Acids Res. 1986 Jan 24;14(2):659–673. doi: 10.1093/nar/14.2.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen L. B., Herner A. E., Goldberg I. H. Inhibition by pactamycin of the initiation of protein synthesis. Binding of N-acetylphenylalanyl transfer ribonucleic acid and polyuridylic acid to ribosomes. Biochemistry. 1969 Apr;8(4):1312–1326. doi: 10.1021/bi00832a004. [DOI] [PubMed] [Google Scholar]
  4. Davies J., Cannon M., Mauer M. B. Myomycin: mode of action and mechanism of resistance. J Antibiot (Tokyo) 1988 Mar;41(3):366–372. doi: 10.7164/antibiotics.41.366. [DOI] [PubMed] [Google Scholar]
  5. Delcuve G., Cabezón T., Herzog A., Cannon M., Bollen A. Resistance to the aminoglycoside antibiotic neamine in Escherichia coli. A new mutant whose NeaR phenotype results from the cumulative effects of two distinct mutations. Biochem J. 1978 Jul 15;174(1):1–7. doi: 10.1042/bj1740001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delcuve G., Cabezón T., Herzog A., Cannon M., Bollen A. Resistance to the aminoglycoside antibiotic neamine in Escherichia coli. A new mutant whose NeaR phenotype results from the cumulative effects of two distinct mutations. Biochem J. 1978 Jul 15;174(1):1–7. doi: 10.1042/bj1740001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Moazed D., Noller H. F. Binding of tRNA to the ribosomal A and P sites protects two distinct sets of nucleotides in 16 S rRNA. J Mol Biol. 1990 Jan 5;211(1):135–145. doi: 10.1016/0022-2836(90)90016-F. [DOI] [PubMed] [Google Scholar]
  8. Moazed D., Noller H. F. Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA. Biochimie. 1987 Aug;69(8):879–884. doi: 10.1016/0300-9084(87)90215-x. [DOI] [PubMed] [Google Scholar]
  9. Moazed D., Noller H. F. Interaction of antibiotics with functional sites in 16S ribosomal RNA. Nature. 1987 Jun 4;327(6121):389–394. doi: 10.1038/327389a0. [DOI] [PubMed] [Google Scholar]
  10. Moazed D., Noller H. F. Interaction of tRNA with 23S rRNA in the ribosomal A, P, and E sites. Cell. 1989 May 19;57(4):585–597. doi: 10.1016/0092-8674(89)90128-1. [DOI] [PubMed] [Google Scholar]
  11. Moazed D., Noller H. F. Transfer RNA shields specific nucleotides in 16S ribosomal RNA from attack by chemical probes. Cell. 1986 Dec 26;47(6):985–994. doi: 10.1016/0092-8674(86)90813-5. [DOI] [PubMed] [Google Scholar]
  12. Montandon P. E., Wagner R., Stutz E. E. coli ribosomes with a C912 to U base change in the 16S rRNA are streptomycin resistant. EMBO J. 1986 Dec 20;5(13):3705–3708. doi: 10.1002/j.1460-2075.1986.tb04703.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Okuyama A., Machiyama N., Kinoshita T., Tanaka N. Inhibition by kasugamycin of initiation complex formation on 30S ribosomes. Biochem Biophys Res Commun. 1971 Apr 2;43(1):196–199. doi: 10.1016/s0006-291x(71)80106-7. [DOI] [PubMed] [Google Scholar]
  14. Perzynski S., Cannon M., Cundliffe E., Chahwala S. B., Davies J. Effects of apramycin, a novel aminoglycoside antibiotic on bacterial protein synthesis. Eur J Biochem. 1979 Sep;99(3):623–628. doi: 10.1111/j.1432-1033.1979.tb13295.x. [DOI] [PubMed] [Google Scholar]
  15. Stern S., Moazed D., Noller H. F. Structural analysis of RNA using chemical and enzymatic probing monitored by primer extension. Methods Enzymol. 1988;164:481–489. doi: 10.1016/s0076-6879(88)64064-x. [DOI] [PubMed] [Google Scholar]
  16. Stern S., Powers T., Changchien L. M., Noller H. F. RNA-protein interactions in 30S ribosomal subunits: folding and function of 16S rRNA. Science. 1989 May 19;244(4906):783–790. doi: 10.1126/science.2658053. [DOI] [PubMed] [Google Scholar]
  17. Tai P. C., Wallace B. J., Davis B. D. Actions of aurintricarboxylate, kasugamycin, and pactamycin on Escherichia coli polysomes. Biochemistry. 1973 Feb;12(4):616–620. doi: 10.1021/bi00728a008. [DOI] [PubMed] [Google Scholar]

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