{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:55:32Z","timestamp":1790826932229,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["MRF-145-0004-TPG-AVISO"],"award-info":[{"award-number":["MRF-145-0004-TPG-AVISO"]}],"id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/S50676X\/1"],"award-info":[{"award-number":["BB\/S50676X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["European Lead factory and ENABLE components"],"award-info":[{"award-number":["European Lead factory and ENABLE components"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Resistance to \u03b2-lactam antibacterials, importantly via production of \u03b2-lactamases, threatens their widespread use. Bicyclic boronates show promise as clinically useful, dual-action inhibitors of both serine- (SBL) and metallo- (MBL) \u03b2-lactamases. In combination with cefepime, the bicyclic boronate taniborbactam is in phase 3 clinical trials for treatment of complicated urinary tract infections. We report kinetic and crystallographic studies on the inhibition of AmpC, the class C \u03b2-lactamase from Escherichia coli, by bicyclic boronates, including taniborbactam, with different C-3 side chains. The combined studies reveal that an acylamino side chain is not essential for potent AmpC inhibition by active site binding bicyclic boronates. The tricyclic form of taniborbactam was observed bound to the surface of crystalline AmpC, but not at the active site, where the bicyclic form was observed. Structural comparisons reveal insights into why active site binding of a tricyclic form has been observed with the NDM-1 MBL, but not with other studied \u03b2-lactamases. Together with reported studies on the structural basis of inhibition of class A, B and D \u03b2-lactamases, our data support the proposal that bicyclic boronates are broad-spectrum \u03b2-lactamase inhibitors that work by mimicking a high energy \u2018tetrahedral\u2019 intermediate. These results suggest further SAR guided development could improve the breadth of clinically useful \u03b2-lactamase inhibition.<\/jats:p>","DOI":"10.3390\/biom10060899","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T12:16:57Z","timestamp":1592223417000},"page":"899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C \u03b2-Lactamase from Escherichia coli"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-1469","authenticated-orcid":false,"given":"Pauline A.","family":"Lang","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anete","family":"Parkova","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Leissing","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-4645","authenticated-orcid":false,"given":"Karina","family":"Calvopi\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Cain","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7822-1944","authenticated-orcid":false,"given":"Alen","family":"Krajnc","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-1336","authenticated-orcid":false,"given":"Tharindi D.","family":"Panduwawala","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Philippe","sequence":"additional","affiliation":[{"name":"Jacobs University Bremen gGmbH, 28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin W. G.","family":"Fishwick","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peteris","family":"Trapencieris","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0276-8174","authenticated-orcid":false,"given":"Malcolm G. P.","family":"Page","sequence":"additional","affiliation":[{"name":"Jacobs University Bremen gGmbH, 28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0290-6565","authenticated-orcid":false,"given":"Christopher J.","family":"Schofield","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0137-3226","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Brem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford OX1 3TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S1473-3099(14)70071-4","article-title":"Antibiotic use in eastern Europe: A cross-national database study in coordination with the WHO Regional Office for Europe","volume":"14","author":"Versporten","year":"2014","journal-title":"Lancet Infect. 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