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Emerging evidence shows that the elongation factor EF-Tu could be an excellent target for treating Mtb infection. Here, we report the crystal structures of Mtb EF-Tu\u2022EF-Ts and EF-Tu\u2022GDP complexes, showing the molecular basis of EF-Tu\u2019s representative recycling and inactive forms in protein translation. Mtb EF-Tu binds with EF-Ts at a 1:1 ratio in solution and crystal packing. Mutation and SAXS analysis show that EF-Ts residues Arg13, Asn82, and His149 are indispensable for the EF-Tu\/EF-Ts complex formation. The GDP binding pocket of EF-Tu dramatically changes conformations upon binding with EF-Ts, sharing a similar GDP-exchange mechanism in<jats:italic>E. coli<\/jats:italic>and<jats:italic>T. ther<\/jats:italic>. Also, the FDA-approved drug Osimertinib inhibits the growth of<jats:italic>M. smegmatis<\/jats:italic>, H37Ra, and<jats:italic>M. bovis<\/jats:italic>BCG strains by directly binding with EF-Tu. Thus, our work reveals the structural basis of Mtb EF-Tu in polypeptide synthesis and may provide a promising candidate for TB treatment.<\/jats:p>","DOI":"10.1038\/s42003-022-04019-y","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T15:03:01Z","timestamp":1664809381000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Structural insights of the elongation factor EF-Tu complexes in protein translation of Mycobacterium tuberculosis"],"prefix":"10.1038","volume":"5","author":[{"given":"Bowen","family":"Zhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-8852","authenticated-orcid":false,"given":"Jianhua","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-3175","authenticated-orcid":false,"given":"Jixi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"4019_CR1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.drudis.2021.09.003","volume":"27","author":"L Yang","year":"2022","unstructured":"Yang, L. et al. 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