{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:26:19Z","timestamp":1768825579428,"version":"3.49.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"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":[[2011,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial resistance to \u03b2-lactam antibiotics (penicillins, cephalosporins, carbapenems, etc.) is commonly the result of the production of \u03b2-lactamases. The emergence of \u03b2-lactamases capable of turning over carbapenem antibiotics is of great concern, since these are often considered the last resort antibiotics in the treatment of life-threatening infections. \u03b2-Lactamases of the GES family are extended-spectrum enzymes that include members that have acquired carbapenemase activity through a single amino acid substitution at position 170. We investigated inhibition of the GES-1, -2, and -5 \u03b2-lactamases by the clinically important \u03b2-lactamase inhibitor clavulanic acid. While GES-1 and -5 are susceptible to inhibition by clavulanic acid, GES-2 shows the greatest susceptibility. This is the only variant to possess the canonical asparagine at position 170. The enzyme with asparagine, as opposed to glycine (GES-1) or serine (GES-5), then leads to a higher affinity for clavulanic acid (\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            = 5 \u03bcM), a higher rate constant for inhibition, and a lower partition ratio (\n            <jats:italic>r<\/jats:italic>\n            \u2248 20). Asparagine at position 170 also results in the formation of stable complexes, such as a cross-linked species and a hydrated aldehyde. In contrast, serine at position 170 leads to formation of a long-lived\n            <jats:italic>trans<\/jats:italic>\n            -enamine species. These studies provide new insight into the importance of the residue at position 170 in determining the susceptibility of GES enzymes to clavulanic acid.\n          <\/jats:p>","DOI":"10.1128\/aac.01292-10","type":"journal-article","created":{"date-parts":[[2011,1,11]],"date-time":"2011-01-11T04:25:08Z","timestamp":1294719908000},"page":"1556-1562","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Importance of Position 170 in the Inhibition of GES-Type \u03b2-Lactamases by Clavulanic Acid"],"prefix":"10.1128","volume":"55","author":[{"given":"Hilary","family":"Frase","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Toth","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M.","family":"Champion","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuno T.","family":"Antunes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei B.","family":"Vakulenko","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"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":"10.1016\/S0167-4838(01)00175-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.933-951.2001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi961044g"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.851"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1323"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/278360a0"},{"key":"e_1_3_2_10_2","unstructured":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard 2006"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0550170"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-09"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr030102i"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.011262"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/432803"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00961-09"},{"key":"e_1_3_2_17_2","first-page":"145","volume":"13","year":"1987","unstructured":"Grace, M. 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