{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:00:45Z","timestamp":1792458045635,"version":"4.5.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,7,3]]},"abstract":"<jats:p>\n                    Aminoglycosides are potent antibacterials, but therapy is compromised by substantial toxicity causing, in particular, irreversible hearing loss. Aminoglycoside ototoxicity occurs both in a sporadic dose-dependent and in a genetically predisposed fashion. We recently have developed a mechanistic concept that postulates a key role for the mitochondrial ribosome (mitoribosome) in aminoglycoside ototoxicity. We now report on the surprising finding that apramycin, a structurally unique aminoglycoside licensed for veterinary use, shows little activity toward eukaryotic ribosomes, including hybrid ribosomes which were genetically engineered to carry the mitoribosomal aminoglycoside-susceptibility A1555G allele. In ex vivo cultures of cochlear explants and in the in vivo guinea pig model of chronic ototoxicity, apramycin causes only little hair cell damage and hearing loss but it is a potent antibacterial with good activity against a range of clinical pathogens, including multidrug-resistant\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    . These data provide proof of concept that antibacterial activity can be dissected from aminoglycoside ototoxicity. Together with 3D structures of apramycin-ribosome complexes at 3.5-\u00c5 resolution, our results provide a conceptual framework for further development of less toxic aminoglycosides by hypothesis-driven chemical synthesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1204073109","type":"journal-article","created":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T01:27:32Z","timestamp":1339723652000},"page":"10984-10989","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":209,"title":["Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin"],"prefix":"10.1073","volume":"109","author":[{"given":"Tanja","family":"Matt","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, 8006 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyan Leong","family":"Ng","sequence":"additional","affiliation":[{"name":"Structural Studies Division, Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Lang","sequence":"additional","affiliation":[{"name":"Structural Studies Division, Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hua","family":"Sha","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Akbergenov","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, 8006 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Shcherbakov","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, 8006 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, 8006 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Duscha","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, 8006 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas R.","family":"Dubbaka","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich, 8093 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9borah","family":"Perez-Fernandez","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich, 8093 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vasella","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Organische Chemie, Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich, 8093 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Structural Studies Division, Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Schacht","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C.","family":"B\u00f6ttger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Universit\u00e4t Z\u00fcrich, 8006 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,6,14]]},"reference":[{"key":"e_1_3_4_1_2","volume-title":"The Molecular Basis of Antibiotic Action","author":"Gale EF","year":"1981","unstructured":"EF Gale, E Cundliffe, PE Reynolds, MH Richmond, MJ Waring The Molecular Basis of Antibiotic Action (London, John Wiley and Sons, 2nd Ed, 1981).","edition":"2"},{"key":"e_1_3_4_2_2","volume-title":"Goodman and Gilman's The Pharmaceutical Basis of Therapeutics","author":"Chambers HF","year":"1996","unstructured":"HF Chambers, Chemotherapy of microbial diseases. Goodman and Gilman's The Pharmaceutical Basis of Therapeutics (McGraw-Hill, 10th Ed, New York, 1996).","edition":"10"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/327389a0","article-title":"Interaction of antibiotics with functional sites in 16S ribosomal RNA","volume":"327","author":"Moazed D","year":"1987","unstructured":"D Moazed, HF Noller, Interaction of antibiotics with functional sites in 16S ribosomal RNA. Nature 327, 389\u2013394 (1987).","journal-title":"Nature"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0026-895X(25)14722-6","article-title":"Misreading of RNA codewords induced by aminoglycoside antibiotics","volume":"1","author":"Davies JL","year":"1965","unstructured":"JL Davies, L Gorini, BD Davis, Misreading of RNA codewords induced by aminoglycoside antibiotics. Mol Pharmacol 1, 93\u2013106 (1965).","journal-title":"Mol Pharmacol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1128\/AAC.4.4.402","article-title":"Structure-activity relationships among the aminoglycoside antibiotics: Role of hydroxyl and amino groups","volume":"4","author":"Benveniste R","year":"1973","unstructured":"R Benveniste, J Davies, Structure-activity relationships among the aminoglycoside antibiotics: Role of hydroxyl and amino groups. Antimicrob Agents Chemother 4, 402\u2013409 (1973).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/0006-291X(78)91493-6","article-title":"Inhibition of ribosomal translocation by aminoglycoside antibiotics","volume":"83","author":"Caba\u00f1as MJ","year":"1978","unstructured":"MJ Caba\u00f1as, D V\u00e1zquez, J Modolell, Inhibition of ribosomal translocation by aminoglycoside antibiotics. Biochem Biophys Res Commun 83, 991\u2013997 (1978).","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/72364","article-title":"Conformational switch in the decoding region of 16S rRNA during aminoacyl-tRNA selection on the ribosome","volume":"7","author":"Pape T","year":"2000","unstructured":"T Pape, W Wintermeyer, MV Rodnina, Conformational switch in the decoding region of 16S rRNA during aminoacyl-tRNA selection on the ribosome. Nat Struct Biol 7, 104\u2013107 (2000).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.jmb.2004.08.097","article-title":"Conformational changes of the small ribosomal subunit during elongation factor G-dependent tRNA-mRNA translocation","volume":"343","author":"Peske F","year":"2004","unstructured":"F Peske, A Savelsbergh, VI Katunin, MV Rodnina, W Wintermeyer, Conformational changes of the small ribosomal subunit during elongation factor G-dependent tRNA-mRNA translocation. J Mol Biol 343, 1183\u20131194 (2004).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nchembio.274","article-title":"Aminoglycoside activity observed on single pre-translocation ribosome complexes","volume":"6","author":"Feldman MB","year":"2010","unstructured":"MB Feldman, DS Terry, RB Altman, SC Blanchard, Aminoglycoside activity observed on single pre-translocation ribosome complexes. Nat Chem Biol 6, 54\u201362 (2010).","journal-title":"Nat Chem Biol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/35030019","article-title":"Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics","volume":"407","author":"Carter AP","year":"2000","unstructured":"AP Carter, et al., Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407, 340\u2013348 (2000).","journal-title":"Nature"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0969-2126(01)00629-3","article-title":"Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site","volume":"9","author":"Vicens Q","year":"2001","unstructured":"Q Vicens, E Westhof, Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site. Structure 9, 647\u2013658 (2001).","journal-title":"Structure"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1093\/nar\/gki862","article-title":"Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: Role of the number of rings and positive charges in the specific binding leading to miscoding","volume":"33","author":"Fran\u00e7ois B","year":"2005","unstructured":"B Fran\u00e7ois, et al., Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: Role of the number of rings and positive charges in the specific binding leading to miscoding. Nucleic Acids Res 33, 5677\u20135690 (2005).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"5112","DOI":"10.1128\/AAC.49.12.5112-5118.2005","article-title":"Analysis of the contribution of individual substituents in 4,6-aminoglycoside-ribosome interaction","volume":"49","author":"Hobbie SN","year":"2005","unstructured":"SN Hobbie, P Pfister, C Br\u00fcll, E Westhof, EC B\u00f6ttger, Analysis of the contribution of individual substituents in 4,6-aminoglycoside-ribosome interaction. Antimicrob Agents Chemother 49, 5112\u20135118 (2005).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/embo-reports\/kve062","article-title":"Structural basis for selectivity and toxicity of ribosomal antibiotics","volume":"2","author":"B\u00f6ttger EC","year":"2001","unstructured":"EC B\u00f6ttger, B Springer, T Prammananan, Y Kidan, P Sander, Structural basis for selectivity and toxicity of ribosomal antibiotics. EMBO Rep 2, 318\u2013323 (2001).","journal-title":"EMBO Rep"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s00018-007-6431-5","article-title":"Antimicrobial agents targeting the ribosome: The issue of selectivity and toxicity - lessons to be learned","volume":"64","author":"B\u00f6ttger EC","year":"2007","unstructured":"EC B\u00f6ttger, Antimicrobial agents targeting the ribosome: The issue of selectivity and toxicity - lessons to be learned. Cell Mol Life Sci 64, 791\u2013795 (2007).","journal-title":"Cell Mol Life Sci"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1261\/rna.805208","article-title":"Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity","volume":"14","author":"Fan-Minogue H","year":"2008","unstructured":"H Fan-Minogue, DM Bedwell, Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity. RNA 14, 148\u2013157 (2008).","journal-title":"RNA"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000013861","article-title":"Aminoglycoside antibiotics","volume":"5","author":"Forge A","year":"2000","unstructured":"A Forge, J Schacht, Aminoglycoside antibiotics. Audiol Neurootol 5, 3\u201322 (2000).","journal-title":"Audiol Neurootol"},{"key":"e_1_3_4_18_2","volume-title":"Aminoglycoside Antibiotics","author":"Davies J","year":"2007","unstructured":"J Davies, In the beginning there was streptomycin. Aminoglycoside Antibiotics (John Wiley & Sons, Hoboken, NJ, 2007)."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/ng0793-289","article-title":"Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness","volume":"4","author":"Prezant TR","year":"1993","unstructured":"TR Prezant, et al., Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 4, 289\u2013294 (1993).","journal-title":"Nat Genet"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.heares.2011.05.008","article-title":"New developments in aminoglycoside therapy and ototoxicity","volume":"281","author":"Xie J","year":"2011","unstructured":"J Xie, AE Talaska, J Schacht, New developments in aminoglycoside therapy and ototoxicity. Hear Res 281, 28\u201337 (2011).","journal-title":"Hear Res"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1124\/mol.110.068130","article-title":"Aminoglycosides inhibit KCNQ4 channels in cochlear outer hair cells via depletion of phosphatidylinositol(4,5)bisphosphate","volume":"79","author":"Leitner MG","year":"2011","unstructured":"MG Leitner, CR Halaszovich, D Oliver, Aminoglycosides inhibit KCNQ4 channels in cochlear outer hair cells via depletion of phosphatidylinositol(4,5)bisphosphate. Mol Pharmacol 79, 51\u201360 (2011).","journal-title":"Mol Pharmacol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/nm1296-1338","article-title":"N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss","volume":"2","author":"Basile AS","year":"1996","unstructured":"AS Basile, et al., N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss. Nat Med 2, 1338\u20131343 (1996).","journal-title":"Nat Med"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1097\/00001756-199812010-00023","article-title":"Are aminoglycoside antibiotics excitotoxic?","volume":"9","author":"Sha SH","year":"1998","unstructured":"SH Sha, J Schacht, Are aminoglycoside antibiotics excitotoxic? Neuroreport 9, 3893\u20133895 (1998).","journal-title":"Neuroreport"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1073\/pnas.0508053102","article-title":"Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss","volume":"102","author":"Kalinec GM","year":"2005","unstructured":"GM Kalinec, et al., Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss. Proc Natl Acad Sci USA 102, 16019\u201316024 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0378-5955(98)00200-7","article-title":"Stimulation of free radical formation by aminoglycoside antibiotics","volume":"128","author":"Sha SH","year":"1999","unstructured":"SH Sha, J Schacht, Stimulation of free radical formation by aminoglycoside antibiotics. Hear Res 128, 112\u2013118 (1999).","journal-title":"Hear Res"},{"key":"e_1_3_4_26_2","volume-title":"Aminoglycoside Antibiotics","author":"Talaska AE","year":"2007","unstructured":"AE Talaska, J Schacht, Adverse effects of aminoglycoside therapy. Aminoglycoside Antibiotics (John Wiley & Sons, Hoboken, NJ, 2007)."},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1002\/jnr.20833","article-title":"Rac\/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics","volume":"83","author":"Jiang H","year":"2006","unstructured":"H Jiang, SH Sha, J Schacht, Rac\/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics. J Neurosci Res 83, 1544\u20131551 (2006).","journal-title":"J Neurosci Res"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1073\/pnas.0707265105","article-title":"Mitochondrial deafness alleles confer misreading of the genetic code","volume":"105","author":"Hobbie SN","year":"2008","unstructured":"SN Hobbie, et al., Mitochondrial deafness alleles confer misreading of the genetic code. Proc Natl Acad Sci USA 105, 3244\u20133249 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"20888","DOI":"10.1073\/pnas.0811258106","article-title":"Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity","volume":"105","author":"Hobbie SN","year":"2008","unstructured":"SN Hobbie, et al., Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity. Proc Natl Acad Sci USA 105, 20888\u201320893 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.yexmp.2006.09.008","article-title":"Mitochondrial dysfunction and molecular pathways of disease","volume":"83","author":"Pieczenik SR","year":"2007","unstructured":"SR Pieczenik, J Neustadt, Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 83, 84\u201392 (2007).","journal-title":"Exp Mol Pathol"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s12035-010-8123-7","article-title":"Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome","volume":"41","author":"Wu SB","year":"2010","unstructured":"SB Wu, YS Ma, YT Wu, YC Chen, YH Wei, Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome. Mol Neurobiol 41, 256\u2013266 (2010).","journal-title":"Mol Neurobiol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1021\/jo00874a003","article-title":"Apramycin, a unique aminocyclitol antibiotic","volume":"41","author":"O\u2019Connor S","year":"1976","unstructured":"S O\u2019Connor, LK Lam, ND Jones, MO Chaney, Apramycin, a unique aminocyclitol antibiotic. J Org Chem 41, 2087\u20132092 (1976).","journal-title":"J Org Chem"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1093\/jac\/3.6.609","article-title":"The in vitro activity of apramycin, a new aminocyclitol antibiotic","volume":"3","author":"Ryden R","year":"1977","unstructured":"R Ryden, BJ Moore, The in vitro activity of apramycin, a new aminocyclitol antibiotic. J Antimicrob Chemother 3, 609\u2013613 (1977).","journal-title":"J Antimicrob Chemother"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1432-1033.1979.tb13295.x","article-title":"Effects of apramycin, a novel aminoglycoside antibiotic on bacterial protein synthesis","volume":"99","author":"Perzynski S","year":"1979","unstructured":"S Perzynski, M Cannon, E Cundliffe, SB Chahwala, J Davies, Effects of apramycin, a novel aminoglycoside antibiotic on bacterial protein synthesis. Eur J Biochem 99, 623\u2013628 (1979).","journal-title":"Eur J Biochem"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1093\/nar\/gkm658","article-title":"Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria","volume":"35","author":"Hobbie SN","year":"2007","unstructured":"SN Hobbie, et al., Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria. Nucleic Acids Res 35, 6086\u20136093 (2007).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/35030006","article-title":"Structure of the 30S ribosomal subunit","volume":"407","author":"Wimberly BT","year":"2000","unstructured":"BT Wimberly, et al., Structure of the 30S ribosomal subunit. Nature 407, 327\u2013339 (2000).","journal-title":"Nature"},{"key":"e_1_3_4_37_2","first-page":"479","article-title":"A dual-luciferase reporter system for studying recoding signals","volume":"4","author":"Grentzmann GJ","year":"1998","unstructured":"GJ Grentzmann, JA Ingram, PJ Kelly, RF Gesteland, JF Atkins, A dual-luciferase reporter system for studying recoding signals. RNA 4, 479\u2013486 (1998).","journal-title":"RNA"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.jmb.2005.03.025","article-title":"Discrimination between defects in elongation fidelity and termination efficiency provides mechanistic insights into translational readthrough","volume":"348","author":"Salas-Marco J","year":"2005","unstructured":"J Salas-Marco, DM Bedwell, Discrimination between defects in elongation fidelity and termination efficiency provides mechanistic insights into translational readthrough. J Mol Biol 348, 801\u2013815 (2005).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1261\/rna.2201210","article-title":"A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae","volume":"16","author":"Kramer EB","year":"2010","unstructured":"EB Kramer, H Vallabhaneni, LM Mayer, PJ Farabaugh, A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae. RNA 16, 1797\u20131808 (2010).","journal-title":"RNA"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1002\/anie.200500028","article-title":"Molecular recognition by glycoside pseudo base pairs and triples in an apramycin-RNA complex","volume":"44","author":"Han Q","year":"2005","unstructured":"Q Han, et al., Molecular recognition by glycoside pseudo base pairs and triples in an apramycin-RNA complex. Angew Chem Int Ed Engl 44, 2694\u20132700 (2005).","journal-title":"Angew Chem Int Ed Engl"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-1-4615-4897-3_4","article-title":"Aminoglycoside antibiotics. Structures, functions, and resistance","volume":"456","author":"Wright GD","year":"1998","unstructured":"GD Wright, AM Berghuis, S Mobashery, Aminoglycoside antibiotics. Structures, functions, and resistance. Adv Exp Med Biol 456, 27\u201369 (1998).","journal-title":"Adv Exp Med Biol"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/S0140-6736(04)15496-2","article-title":"Programmes and principles in treatment of multidrug-resistant tuberculosis","volume":"363","author":"Mukherjee JS","year":"2004","unstructured":"JS Mukherjee, et al., Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet 363, 474\u2013481 (2004).","journal-title":"Lancet"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/jac\/dkq408","article-title":"Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates","volume":"66","author":"Livermore DM","year":"2011","unstructured":"DM Livermore, et al., Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother 66, 48\u201353 (2011).","journal-title":"J Antimicrob Chemother"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1111\/j.1460-9568.1996.tb01333.x","article-title":"Differential damage to auditory neurons and hair cells by ototoxins and neuroprotection by specific neurotrophins in rat cochlear organotypic cultures","volume":"8","author":"Zheng JL","year":"1996","unstructured":"JL Zheng, WQ Gao, Differential damage to auditory neurons and hair cells by ototoxins and neuroprotection by specific neurotrophins in rat cochlear organotypic cultures. Eur J Neurosci 8, 1897\u20131905 (1996).","journal-title":"Eur J Neurosci"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1111\/j.1471-4159.2009.05871.x","article-title":"Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea","volume":"108","author":"Chen F-Q","year":"2009","unstructured":"F-Q Chen, J Schacht, SH Sha, Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea. J Neurochem 108, 1226\u20131236 (2009).","journal-title":"J Neurochem"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/978-1-4612-4068-6_5","volume-title":"Clinical Aspects of Hearing. Handbook of Auditory Research","author":"Garetz SL","year":"1996","unstructured":"SL Garetz, J Schacht, Ototoxicity: Of mice and men. Clinical Aspects of Hearing. Handbook of Auditory Research, eds TR van de Water, AN Popper, RR Fay (Springer, New York) Vol. 7, 116\u2013154 (1996)."},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(99)00798-0","article-title":"The antibacterial and NMDA receptor activating properties of aminoglycosides are dissociable","volume":"387","author":"Harvey SC","year":"2000","unstructured":"SC Harvey, X Li, P Skolnick, HA Kirst, The antibacterial and NMDA receptor activating properties of aminoglycosides are dissociable. Eur J Pharmacol 387, 1\u20137 (2000).","journal-title":"Eur J Pharmacol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1204073109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T09:01:59Z","timestamp":1743411719000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1204073109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,14]]},"references-count":47,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2012,7,3]]}},"alternative-id":["10.1073\/pnas.1204073109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1204073109","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.723897745.793532054","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,14]]},"assertion":[{"value":"2012-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}