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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,7,5]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The ribosome is the protein-synthesizing machine of the cell and is a major target for antibiotics. The increase in multidrug-resistant bacteria has limited the utility of our current arsenal of clinically used antibiotics, highlighting the need for further development of compounds that have distinct binding sites and do not display cross-resistance. Using cryo-electron microscopy, we have visualized the binding site of the orthosomycins evernimicin and avilamycin on the bacterial 70S ribosome. The binding site and mode of interaction of evernimicin and avilamycin are distinct from other ribosome-targeting antibiotics. Together with single-molecule studies, our structures reveal how the orthosomycin antibiotics inhibit protein synthesis by preventing accommodation of the aminoacyl-tRNA at the A site of the ribosome.<\/jats:p>","DOI":"10.1073\/pnas.1604790113","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T11:32:06Z","timestamp":1466681526000},"page":"7527-7532","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome"],"prefix":"10.1073","volume":"113","author":[{"given":"Stefan","family":"Arenz","sequence":"first","affiliation":[{"name":"Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-8080","authenticated-orcid":false,"given":"Manuel F.","family":"Juette","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Medical College, Cornell University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Graf","sequence":"additional","affiliation":[{"name":"Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Huter","sequence":"additional","affiliation":[{"name":"Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury S.","family":"Polikanov","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607;"},{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60607;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Medical College, Cornell University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Gene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany;"},{"name":"Center for Integrated Protein Science Munich, University of Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,6,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrmicro3155","article-title":"Ribosome-targeting antibiotics and mechanisms of bacterial resistance","volume":"12","author":"Wilson DN","year":"2014","unstructured":"DN Wilson, Ribosome-targeting antibiotics and mechanisms of bacterial resistance. 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