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To address this question, we have investigated the drug binding pockets of aminoglycosides and macrolides\/ketolides. The binding site of aminoglycosides is located within helix 44 of the 16S rRNA (A site); macrolides\/ketolides bind to domain V of the 23S rRNA (peptidyltransferase center). We have used mutagenesis of rRNA sequences in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium smegmatis<\/jats:named-content>ribosomes to reconstruct the different bacterial drug binding sites and to study the effects of rRNA sequence variations on drug activity. Our results provide a rationale for differences in species-specific drug susceptibility patterns and species-specific resistance phenotypes associated with mutational alterations in the drug binding pocket.<\/jats:p>","DOI":"10.1128\/aac.01398-10","type":"journal-article","created":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T03:40:10Z","timestamp":1309923610000},"page":"4096-4102","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Phylogenetic Sequence Variations in Bacterial rRNA Affect Species-Specific Susceptibility to Drugs Targeting Protein Synthesis"],"prefix":"10.1128","volume":"55","author":[{"given":"Subramanian","family":"Akshay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Bertea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven N.","family":"Hobbie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Oettinghaus","sequence":"additional","affiliation":[{"name":"Present address: Centre Universitaire M\u00e9dicale, Universit\u00e9 de Gen\u00e8ve, Rue Michel Servet 1, CH-1211 Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Shcherbakov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C.","family":"B\u00f6ttger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Akbergenov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve062"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35030019"},{"key":"e_1_3_3_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 J.","year":"1965","unstructured":"DaviesJ. 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