{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:56:50Z","timestamp":1789955810801,"version":"4.0.1"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"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":[[2016,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            BEL-1 is an acquired class A extended-spectrum \u03b2-lactamase (ESBL) found in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obtained at pH 5.6, and the structure of native BEL-1 was determined from orthorhombic and monoclinic crystal forms at 1.60-\u212b and 1.48-\u212b resolution, respectively. By soaking native BEL-1 crystals, complexes with imipenem (monoclinic form, 1.79-\u212b resolution) and moxalactam (orthorhombic form, 1.85-\u212b resolution) were also obtained. In the acyl-enzyme complexes, imipenem and moxalactam differ by the position of the \u03b1-substituent and of the carbonyl oxygen (in or out of the oxyanion hole). More surprisingly, the \u03a9-loop, which includes the catalytically relevant residue Glu166, was found in different conformations in the various subunits, resulting in the Glu166 side chain being rotated out of the active site or even in displacement of its C\u03b1 atom up to approximately 10 \u212b. A BEL-1 variant showing the single Leu162Phe substitution (BEL-2) confers a higher level of resistance to CAZ, CTX, and FEP and shows significantly lower\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            values than BEL-1, especially with oxyiminocephalosporins. BEL-1 Leu162 is located at the beginning of the \u03a9-loop and is surrounded by Phe72, Leu139, and Leu148 (contact distances, 3.5 to 3.9 \u212b). This small hydrophobic cavity could not reasonably accommodate the bulkier Phe162 found in BEL-2 without altering neighboring residues or the \u03a9-loop itself, thus likely causing an important alteration of the enzyme kinetic properties.\n          <\/jats:p>","DOI":"10.1128\/aac.00936-16","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T03:44:12Z","timestamp":1474947852000},"page":"7189-7199","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum \u03b2-Lactamase and Its Complexes with Moxalactam and Imipenem"],"prefix":"10.1128","volume":"60","author":[{"given":"Cecilia","family":"Pozzi","sequence":"first","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 di Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"De Luca","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche, Universit\u00e0 di Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Benvenuti","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 di Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Poirel","sequence":"additional","affiliation":[{"name":"INSERM European Unit (LEA), University of Fribourg, Fribourg, Switzerland"},{"name":"Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Nordmann","sequence":"additional","affiliation":[{"name":"INSERM European Unit (LEA), University of Fribourg, Fribourg, Switzerland"},{"name":"Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Maria","family":"Rossolini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche, Universit\u00e0 di Siena, Siena, Italy"},{"name":"SOD Microbiologia e Virologia, Azienda Ospedaliera Universitaria Careggi, Florence, Italy"},{"name":"Dipartimento di Medicina Sperimentale e Clinica, Universit\u00e0 di Firenze, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Mangani","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 di Siena, Siena, Italy"},{"name":"Magnetic Resonance Center CERM, Universit\u00e0 di Firenze, Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Denis","family":"Docquier","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche, Universit\u00e0 di Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01009-09"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01857.x"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3743-3748.2005"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00859-09"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.198"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910048675"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905036693"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0342822"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889897006766"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444911001314"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.91"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444911007281"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00089-14"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3300581"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi972127f"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9818001"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309110054680"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00163-08"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01517-09"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.04.149"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2930607"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00386a014"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja001676x"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi010641m"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205073109"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02247-12"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.485979"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444901019606"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.208744"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi700300u"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.41.26714"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2790213"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003802200"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00400-X"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340230108"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8801"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666151001112859"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg067"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90609-5"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01336-09"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00936-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00936-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:26:27Z","timestamp":1645475187000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00936-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1128\/AAC.00936-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.00936-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]},"assertion":[{"value":"2016-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}