{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:05:20Z","timestamp":1777424720217,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2023,7,2]],"date-time":"2023-07-02T00:00:00Z","timestamp":1688256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["711.016.002"],"award-info":[{"award-number":["711.016.002"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["711.017.013"],"award-info":[{"award-number":["711.017.013"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>\n                    Conserved residues are often considered essential for function, and substitutions in such residues are expected to have a negative influence on the properties of a protein. However, mutations in a few highly conserved residues of the \u03b2\u2010lactamase from\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , BlaC, were shown to have no or only limited negative effect on the enzyme. One such mutant, D179N, even conveyed increased ceftazidime resistance upon bacterial cells, while displaying good activity against penicillins. The crystal structures of BlaC D179N in resting state and in complex with sulbactam reveal subtle structural changes in the \u03a9\u2010loop as compared to the structure of wild\u2010type BlaC. Introducing this mutation in four other \u03b2\u2010lactamases, CTX\u2010M\u201014, KPC\u20102, NMC\u2010A and TEM\u20101, resulted in decreased antibiotic resistance for penicillins and meropenem. The results demonstrate that the Asp in position 179 is generally essential for class A \u03b2\u2010lactamases but not for BlaC, which can be explained by the importance of the interaction with the side chain of Arg164 that is absent in BlaC. It is concluded that Asp179 though conserved is not essential in BlaC, as a consequence of epistasis.\n                  <\/jats:p>","DOI":"10.1111\/febs.16892","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T15:36:05Z","timestamp":1687188965000},"page":"4933-4949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Asp179 in the class A \u03b2\u2010lactamase from\n                    <i>Mycobacterium tuberculosis<\/i>\n                    is a conserved yet not essential residue due to epistasis"],"prefix":"10.1111","volume":"290","author":[{"given":"Ilona","family":"van Alen","sequence":"first","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Chikunova","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny B.","family":"van Zanten","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber A.","family":"de Block","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Timmer","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Br\u00fcnle","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2615-6914","authenticated-orcid":false,"given":"Marcellus","family":"Ubbink","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4328"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2760269"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00320-06"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0342822"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0259640"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02414-21"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.8.1878"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23052"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.04.030"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu081"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00528-17"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.348540"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.633438"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02073-15"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","unstructured":"SunJ ChikunovaA BoyleAL VoskampP TimmerM UbbinkM(2023)Enhanced activity against a third-generation cephalosporin by destabilization of the active site of a class A beta-lactamase. 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