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Aminoglycosides are therefore considered as potential therapies for PTC-associated human diseases. Here, we performed a comprehensive study of the mechanism of action of aminoglycosides in eukaryotes by applying a combination of structural and functional approaches. Our findings reveal complex interactions of aminoglycosides with eukaryotic 80S ribosome caused by their multiple binding sites, which lead to inhibition of intersubunit movement within the human ribosome that impact nearly every aspect of protein synthesis.<\/jats:p>","DOI":"10.1073\/pnas.1715501114","type":"journal-article","created":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T12:10:17Z","timestamp":1512475817000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":222,"title":["Aminoglycoside interactions and impacts on the eukaryotic ribosome"],"prefix":"10.1073","volume":"114","author":[{"given":"Irina","family":"Prokhorova","sequence":"first","affiliation":[{"name":"Department of Integrated Structural Biology, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, INSERM U964, CNRS UMR7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger B.","family":"Altman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muminjon","family":"Djumagulov","sequence":"additional","affiliation":[{"name":"Department of Integrated Structural Biology, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, INSERM U964, CNRS UMR7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya P.","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Urzhumtsev","sequence":"additional","affiliation":[{"name":"Department of Integrated Structural Biology, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, INSERM U964, CNRS UMR7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France;"},{"name":"D\u00e9partement de Physique, Facult\u00e9 des Sciences et des Technologies, Universit\u00e9 de Lorraine, 54506 Vandoeuvre-l\u00e8s-Nancy, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Tri-Institutional PhD Training Program in Chemical Biology, Weill Cornell Medicine, Rockefeller University, Memorial Sloan-Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Wei Tom","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marat","family":"Yusupov","sequence":"additional","affiliation":[{"name":"Department of Integrated Structural Biology, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, INSERM U964, CNRS UMR7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Tri-Institutional PhD Training Program in Chemical Biology, Weill Cornell Medicine, Rockefeller University, Memorial Sloan-Kettering Cancer Center, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara","family":"Yusupova","sequence":"additional","affiliation":[{"name":"Department of Integrated Structural Biology, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, INSERM U964, CNRS UMR7104, Universit\u00e9 de Strasbourg, 67404 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1039\/C4MD00163J","article-title":"New trends in aminoglycosides use","volume":"5","author":"Fosso MY","year":"2014","unstructured":"MY Fosso, Y Li, S Garneau-Tsodikova, New trends in aminoglycosides use. 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Mol Cell 28, 533\u2013543 (2007).","journal-title":"Mol Cell"},{"key":"e_1_3_4_6_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 J","year":"1965","unstructured":"J 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_7_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1126\/science.274.5291.1367","article-title":"Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic","volume":"274","author":"Fourmy D","year":"1996","unstructured":"D Fourmy, MI Recht, SC Blanchard, JD Puglisi, Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. 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