{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:56:49Z","timestamp":1760299009754,"version":"3.33.0"},"reference-count":0,"publisher":"International Union of Crystallography (IUCr)","issue":"10","license":[{"start":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T00:00:00Z","timestamp":1411776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},{"start":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T00:00:00Z","timestamp":1411776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html#TDM"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr D Biol Crystallogr","Acta Crystallogr D","Acta Crystallogr D Biol Cryst","Acta Cryst D","Acta Cryst D Biol Crystallogr","Acta Cryst D Biol Cryst","Acta Cryst Sect D","Acta Cryst Sect D Biol Cryst","Acta Crystallogr Sect D","Acta Crystallogr Sect D Biol Crystallogr"],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:p>Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and enterococcal pathogens is primarily conferred by the bifunctional enzyme AAC(6\u2032)-Ie-APH(2\u2032\u2032)-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6\u2032)-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2\u2032\u2032)-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6\u2032)-Ie-APH(2\u2032\u2032)-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2\u2032\u2032)-Ia enzyme was determined as the binary Mg<jats:sub>2<\/jats:sub>GDP complex. Here, the high-resolution structure of the N-terminal AAC(6\u2032)-Ie enzyme is reported as a ternary kanamycin\/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6\u2032)-Ie enzyme is joined to APH(2\u2032\u2032)-Ia by a short, predominantly rigid linker at the N-terminal end of a long \u03b1-helix. This \u03b1-helix is in turn intrinsically associated with the N-terminus of APH(2\u2032\u2032)-Ia. This structural arrangement supports earlier observations that the presence of the intact \u03b1-helix is essential to the activity of both functionalities of the full-length AAC(6\u2032)-Ie-APH(2\u2032\u2032)-Ia enzyme.<\/jats:p>","DOI":"10.1107\/s1399004714017635","type":"journal-article","created":{"date-parts":[[2014,9,26]],"date-time":"2014-09-26T18:18:29Z","timestamp":1411755509000},"page":"2754-2764","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":17,"title":["Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6\u2032)-Ie-APH(2\u2032\u2032)-Ia revealed by crystallographic and small-angle X-ray scattering analysis"],"prefix":"10.1107","volume":"70","author":[{"given":"Clyde A.","family":"Smith","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Toth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilary","family":"Frase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei B.","family":"Vakulenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2014,9,27]]},"container-title":["Acta Crystallographica Section D Biological Crystallography"],"original-title":[],"link":[{"URL":"http:\/\/journals.iucr.org\/d\/issues\/2014\/10\/00\/mn5069\/mn5069.pdf","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.iucr.org\/d\/issues\/2014\/10\/00\/mn5069\/mn5069.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T09:55:41Z","timestamp":1736762141000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.iucr.org\/paper?S1399004714017635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,27]]},"references-count":0,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10]]}},"alternative-id":["S1399004714017635"],"URL":"https:\/\/doi.org\/10.1107\/s1399004714017635","relation":{},"ISSN":["1399-0047"],"issn-type":[{"type":"electronic","value":"1399-0047"}],"subject":[],"published":{"date-parts":[[2014,9,27]]},"assertion":[{"value":"Acta Crystallographica Section D: Biological Crystallography","name":"journal","label":"Journal","explanation":{"URL":"http:\/\/journals.iucr.org\/d"}},{"value":"research papers","name":"content_type","label":"Content type","explanation":{"URL":"http:\/\/journals.iucr.org\/d\/issues\/2011\/01\/00\/me0434\/index.html"}},{"value":"Yes","order":0,"name":"peer_reviewed","label":"Peer reviewed","group":{"name":"peer_review","label":"Peer review"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review process","group":{"name":"peer_review","label":"Peer review"}},{"value":"6 June 2014","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication history"}},{"value":"31 July 2014","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication history"}},{"value":"27 September 2014","order":2,"name":"published_online","label":"Published online","group":{"name":"publication_history","label":"Publication history"}},{"value":"This article has supporting information","name":"supplementary_materials","label":"Supplementary materials","explanation":{"URL":"http:\/\/scripts.iucr.org\/cgi-bin\/sendsup?mn5069"}},{"value":"\u00a9 2014 International Union of Crystallography","order":0,"name":"copyright","label":"Copyright","explanation":{"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},"group":{"name":"copyright_and_licensing","label":"Copyright and licencing"}}]}}