{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:23:13Z","timestamp":1788621793050,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T00:00:00Z","timestamp":1577750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17K08248"],"award-info":[{"award-number":["17K08248"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>To understand a structural basis for the fitness cost of the A1408G antibiotic-resistance mutation in the ribosomal A-site RNA, we have determined crystal structures of its A1408C and A1408U lethal mutants, and made comparison with previously solved structures of the wild type and the antibiotic-resistant mutant. The A-site RNA containing an asymmetric internal loop functions as a molecular switch to discriminate a single cognate tRNA from several near-cognate tRNAs by its conformational ON\/OFF switching. Overall structures of the \u201coff\u201d states of the A1408C\/U lethal mutants are very similar to those of the wild type and the A1408G antibiotic-resistant mutant. However, significant differences are found in local base stacking interactions including the functionally important A1492 and A1493 residues. In the wild type and the A1408G antibiotic-resistant mutant \u201coff\u201d states, both adenines are exposed to the solvent region. On the other hand, one of the corresponding adenines of the lethal A1408C\/U mutants stay deeply inside their A-site helices by forming a purine-pyrimidine AoC or A-U base pair and is sandwiched between the upper and lower bases. Therefore, the ON\/OFF switching might unfavorably occur in the lethal mutants compared to the wild type and the A1408G antibiotic-resistant mutant. It is probable that bacteria manage to acquire antibiotic resistance without losing the function of the A-site molecular switch by mutating the position 1408 only from A to G, but not to pyrimidine base C or U.<\/jats:p>","DOI":"10.3390\/molecules25010159","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T03:28:53Z","timestamp":1578022133000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structural Bases for the Fitness Cost of the Antibiotic-Resistance and Lethal Mutations at Position 1408 of 16S rRNA"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-3685","authenticated-orcid":false,"given":"Jiro","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo 102-8554, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Koganei","sequence":"additional","affiliation":[{"name":"Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo 102-8554, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0968-0004(03)00066-5","article-title":"Insights into the decoding mechanism from recent ribosome structure","volume":"28","author":"Ogle","year":"2003","journal-title":"Trends Biochem. 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