{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:56:22Z","timestamp":1789577782980,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI100560, R01AI063517, and R01AI072219"],"award-info":[{"award-number":["R01AI100560, R01AI063517, and R01AI072219"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX002872 to K.M.P.-W. and 1I01BX001974 to R.A.B."],"award-info":[{"award-number":["1I01BX002872 to K.M.P.-W. and 1I01BX001974 to R.A.B."]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Boronic acid transition-state analog inhibitors (BATSIs) are partners with \u03b2-lactam antibiotics for the treatment of complex bacterial infections. Herein, microbiological, biochemical, and structural findings on four BATSIs with the FOX-4 cephamycinase, a class C \u03b2-lactamase that rapidly hydrolyzes cefoxitin, are revealed. FOX-4 is an extended-spectrum class C cephalosporinase that demonstrates conformational flexibility when complexed with certain ligands. Like other \u03b2-lactamases of this class, studies on FOX-4 reveal important insights into structure\u2013activity relationships. We show that SM23, a BATSI, shows both remarkable flexibility and affinity, binding similarly to other \u03b2-lactamases, yet retaining an IC50 value &lt; 0.1 \u03bcM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes.<\/jats:p>","DOI":"10.3390\/biom10050671","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T10:30:58Z","timestamp":1588069858000},"page":"671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Structures of FOX-4 Cephamycinase in Complex with Transition-State Analog Inhibitors"],"prefix":"10.3390","volume":"10","author":[{"given":"Scott T.","family":"Lefurgy","sequence":"first","affiliation":[{"name":"Department of Chemistry, Hofstra University, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-9453","authenticated-orcid":false,"given":"Emilia","family":"Caselli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena A.","family":"Taracila","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir N.","family":"Malashkevich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena","family":"Biju","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hofstra University, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina M.","family":"Papp-Wallace","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA"},{"name":"Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Bonanno","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Prati","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Almo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA"},{"name":"Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Department of Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES) Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1128\/AAC.00296-11","article-title":"Carbapenems: Past, Present, and Future","volume":"55","author":"Endimiani","year":"2011","journal-title":"Antimicrob. 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