{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:02:08Z","timestamp":1789732928830,"version":"4.0.1"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            GES-1 is a class A extended-spectrum \u03b2-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>cat<\/jats:sub>\n            values for carbapenems. Twenty-two GES variants have been discovered thus far, differing from each other by 1 to 3 amino acid substitutions that affect substrate specificity. GES-11 possesses a Gly243Ala substitution which seems to confer to this variant an increased activity against aztreonam and ceftazidime. GES-12 differs from GES-11 by a single Thr237Ala substitution, while GES-14 differs from GES-11 by the Gly170Ser mutation, which is known to confer increased carbapenemase activity. GES-11 and GES-12 were kinetically characterized and compared to GES-1 and GES-14. Purified GES-11 and GES-12 showed strong activities against most tested \u03b2-lactams, with the exception of temocillin, cefoxitin, and carbapenems. Both variants showed a significantly increased rate of hydrolysis of cefotaxime, ceftazidime, and aztreonam. On the other hand, GES-11 and GES-12 (and GES-14) variants all containing Ala243 exhibited increased susceptibility to classical inhibitors. The crystallographic structures of the GES-11 and GES-14 \u03b2-lactamases were solved. The overall structures of GES-11 and GES-14 are similar to that of GES-1. The Gly243Ala substitution caused only subtle local rearrangements, notably in the typical carbapenemase disulfide bond. The active sites of GES-14 and GES-11 are very similar, with the Gly170Ser substitution leading only to the formation of additional hydrogen bonds of the Ser residue with hydrolytic water and the Glu166 residue.\n          <\/jats:p>","DOI":"10.1128\/aac.01272-12","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T04:22:25Z","timestamp":1345522945000},"page":"5618-5625","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Kinetic and Crystallographic Studies of Extended-Spectrum GES-11, GES-12, and GES-14 \u03b2-Lactamases"],"prefix":"10.1128","volume":"56","author":[{"given":"Heinrich","family":"Delbr\u00fcck","sequence":"first","affiliation":[{"name":"Institute of Molecular Biotechnology, RWTH-Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Bogaerts","sequence":"additional","affiliation":[{"name":"Reference Laboratory for Monitoring of Antimicrobial Resistance in Gram-Negative Bacteria, Cliniques Universitaires de Mont-Godinne, Universit\u00e9 Catholique de Louvain, Yvoir, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u00ebl B.","family":"Kupper","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, RWTH-Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rezende de Castro","sequence":"additional","affiliation":[{"name":"Reference Laboratory for Monitoring of Antimicrobial Resistance in Gram-Negative Bacteria, Cliniques Universitaires de Mont-Godinne, Universit\u00e9 Catholique de Louvain, Yvoir, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bennink","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, RWTH-Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youri","family":"Glupczynski","sequence":"additional","affiliation":[{"name":"Reference Laboratory for Monitoring of Antimicrobial Resistance in Gram-Negative Bacteria, Cliniques Universitaires de Mont-Godinne, Universit\u00e9 Catholique de Louvain, Yvoir, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moreno","family":"Galleni","sequence":"additional","affiliation":[{"name":"Biological Macromolecules, Centre for Protein Engineering, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt M.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, RWTH-Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Bebrone","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology, RWTH-Aachen University, Aachen, Germany"},{"name":"Biological Macromolecules, Centre for Protein Engineering, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2760269"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2007.02.013"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00871-10"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00773-10"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.208744"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01292-10"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.1259"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/prot.340060310","article-title":"Substrate specificities in class A beta-lactamases: preference for penams versus cephems. 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Binding of cephalothin and cefotaxime to d-ala-d-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. 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Structure of GES-1 at atomic resolution: insights into the evolution of carbapenemase activity in the class A extended-spectrum \u03b2-lactamases. Acta Crystallogr. D Biol. Crystallogr. 63:982\u2013992.","journal-title":"Acta Crystallogr. D Biol. 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