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Using rapid\u2010mixing methods, we studied the transient kinetics of aminoglycoside phosphotransferase(3\u2032)\u2010IIIa. We show that an ADP\u2010enzyme complex is the main steady state intermediate. This intermediate interacts strongly with kanamycin A to form an abortive complex that traps the enzyme in an inactive state. A good strategy to prevent the inactivation of aminoglycosides would be to develop uncompetitive inhibitors that interact with this key ADP\u2010enzyme complex.<\/jats:p>","DOI":"10.1016\/j.febslet.2012.10.027","type":"journal-article","created":{"date-parts":[[2012,10,26]],"date-time":"2012-10-26T19:00:21Z","timestamp":1351278021000},"page":"4223-4227","source":"Crossref","is-referenced-by-count":12,"title":["Transient kinetics of aminoglycoside phosphotransferase(3\u2032)\u2010IIIa reveals a potential drug target in the antibiotic resistance mechanism"],"prefix":"10.1002","volume":"586","author":[{"given":"Perrine","family":"Lallemand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Leban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Kunzelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Chaloin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engin H.","family":"Serpersu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Barman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Lionne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-8-123"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.03.063"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(96)90251-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(86)81424-7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.12.3249-3256.2000"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.437"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4897-3_4"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100540200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00062-09"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.42.24686"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9603884"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.03.061"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6243-z"},{"key":"e_1_2_6_15_1","unstructured":"H. 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