{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:24:36Z","timestamp":1790529876336,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Aminoglycoside 2\u2033-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci. We describe a novel aminoglycoside 2\u2033-phosphotransferase from the Gram-negative pathogen\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Campylobacter jejuni<\/jats:named-content>\n            , which shares 78% amino acid sequence identity with the APH(2\u2033)-Ia domain of the bifunctional aminoglycoside-modifying enzyme aminoglycoside (6\u2032) acetyltransferase-Ie\/aminoglycoside 2\u2033-phosphotransferase-Ia or AAC(6\u2032)-Ie\/APH(2\u2033)-Ia from Gram-positive cocci, which we called APH(2\u2033)-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin, but not to any of the 4,5-disubstituted antibiotics tested. Steady-state kinetic studies demonstrated that GTP, and not ATP, is the preferred cosubstrate for APH(2\u2033)-If. The enzyme phosphorylates the majority of 4,6-disubstituted aminoglycosides with high catalytic efficiencies (\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>cat<\/jats:sub>\n            \/\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            = 10\n            <jats:sup>5<\/jats:sup>\n            to 10\n            <jats:sup>7<\/jats:sup>\n            M\n            <jats:sup>\u22121<\/jats:sup>\n            s\n            <jats:sup>\u22121<\/jats:sup>\n            ), while the catalytic efficiencies against the 4,6-disubstituted antibiotics amikacin and isepamicin are 1 to 2 orders of magnitude lower, due mainly to the low apparent affinities of these substrates for the enzyme. Both 4,5-disubstituted antibiotics and the atypical aminoglycoside neamine are not substrates of APH(2\u2033)-If, but are inhibitors. The antibiotic susceptibility and substrate profiles of APH(2\u2033)-If are very similar to those of the APH(2\u2033)-Ia phosphotransferase domain of the bifunctional AAC(6\u2032)-Ie\/APH(2\u2033)-Ia enzyme.\n          <\/jats:p>","DOI":"10.1128\/aac.02049-12","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T05:32:19Z","timestamp":1352179939000},"page":"452-457","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Novel Aminoglycoside 2\u2033-Phosphotransferase Identified in a Gram-Negative Pathogen"],"prefix":"10.1128","volume":"57","author":[{"given":"Marta","family":"Toth","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Frase","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno T.","family":"Antunes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei B.","family":"Vakulenko","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4897-3_4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.5.1546-1549.2002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/327389a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060612"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.16.3.430-450.2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/520991"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2008.09.001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.2011.02452.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.15.1.7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/28.1.1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2624"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3375-3380.2001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.3.465"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.3.398"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-73-1-175"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.120.3.1293-1299.1974"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(87)90349-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-007-0331-9"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/518605"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2010.08.003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/313949"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709645200"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808148200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.437"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi6024512"},{"key":"e_1_3_2_27_2","unstructured":"Clinical and Laboratory Standards Institute. 2009. 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