{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:48:25Z","timestamp":1790711305177,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,12]],"date-time":"2020-09-12T00:00:00Z","timestamp":1599868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201017\u2010CE11\u20100008\u201001"],"award-info":[{"award-number":["ANR\u201017\u2010CE11\u20100008\u201001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DEQ20150331719"],"award-info":[{"award-number":["DEQ20150331719"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Enhanced intracellular survival (Eis) proteins belonging to the superfamily of the GCN5\u2010related\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyltransferases play important functions in mycobacterial pathogenesis. In\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , Eis enhances the intracellular survival of the bacilli in macrophages by modulating the host immune response and is capable to chemically modify and inactivate aminoglycosides. In nontuberculous mycobacteria (NTM), Eis shares similar functions. However,\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    , a multidrug resistant NTM, possesses two functionally distinct Eis homologues, Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    and Eis2\n                    <jats:sub>Mab<\/jats:sub>\n                    . While Eis2\n                    <jats:sub>Mab<\/jats:sub>\n                    participates in virulence and aminoglycosides resistance, this is not the case for Eis1\n                    <jats:sub>Mab,<\/jats:sub>\n                    whose exact biological function remains to be determined. Herein, we show that overexpression of Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    in\n                    <jats:italic>M. abscessus<\/jats:italic>\n                    fails to induce resistance to aminoglycosides. To clarify why Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    is unable to modify this class of antibiotics, we solved its crystal structure bound to its cofactor, acetyl\u2010CoA. The structure revealed that Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    has a typical homohexameric Eis\u2010like organization. The structural analysis supported by biochemical approaches demonstrated that while Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    can acetylate small substrates, its active site is too narrow to accommodate aminoglycosides. Comparison with other Eis structures showed that an extended loop between strands 9 and 10 is blocking the access of large substrates to the active site and movement of helices 4 and 5 reduces the volume of the substrate\u2010binding pocket to these compounds in Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    . Overall, this study underscores the molecular determinants explaining functional differences between Eis1\n                    <jats:sub>Mab<\/jats:sub>\n                    and Eis2\n                    <jats:sub>Mab,<\/jats:sub>\n                    especially those inherent to their capacity to modify aminoglycosides.\n                  <\/jats:p>","DOI":"10.1002\/prot.25997","type":"journal-article","created":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T01:51:47Z","timestamp":1598665907000},"page":"94-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Structural analysis of the\n                    <i>N<\/i>\n                    \u2010acetyltransferase Eis1 from\n                    <i>Mycobacterium abscessus<\/i>\n                    reveals the molecular determinants of its incapacity to modify aminoglycosides"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4896-774X","authenticated-orcid":false,"given":"Kien Lam","family":"Ung","sequence":"first","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier (IRIM) Universit\u00e9 de Montpellier, CNRS UMR  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-4458","authenticated-orcid":false,"given":"Laurent","family":"Kremer","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier (IRIM) Universit\u00e9 de Montpellier, CNRS UMR  Montpellier France"},{"name":"INSERM, IRIM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7860-3464","authenticated-orcid":false,"given":"Micka\u00ebl","family":"Blaise","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Infectiologie de Montpellier (IRIM) Universit\u00e9 de Montpellier, CNRS UMR  Montpellier 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