{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:53:28Z","timestamp":1790434408068,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T00:00:00Z","timestamp":1230681600000},"content-version":"vor","delay-in-days":4048,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[1997,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The metallo\u2010\u03b2\u2010lactamases require zinc or cadmium for hydrolyzing \u03b2\u2010lactam antibiotics and are inhibited by mercurial compounds. To date, there are no clinically useful inhibitors of this class of enzymes. The crystal structure of the Zn<jats:sup>2+<\/jats:sup>\u2010bound enzyme from <jats:italic>Bacteroides fragilis<\/jats:italic> contains a binuclear zinc center in the active site. A hydroxide, coordinated to both zinc atoms, is proposed as the moiety that mounts the nucleophilic attack on the carbonyl carbon atom of the \u03b2\u2010lactam ring. To study the metal coordination further, the crystal structures of a Cd<jats:sup>2+<\/jats:sup>\u2010bound enzyme and of an Hg<jats:sup>2+<\/jats:sup>\u2010soaked zinc\u2010containing enzyme have been determined at 2.I \u00c5 and 2.7 \u00c5, respectively. Given the diffraction resolution, the Cd<jats:sup>2+<\/jats:sup>\u2010bound enzyme exhibits the same active\u2010site architecture as that of the Zn<jats:sup>2+<\/jats:sup>\u2010bound enzyme, consistent with the fact that both forms are enzymatically active. The 10\u2010fold reduction in activity of the Cd<jats:sup>2+<\/jats:sup>\u2010bound molecule compared with the Zn<jats:sup>2+<\/jats:sup>\u2010bound enzyme is attributed to fine differences in the charge distribution due to the difference in the ionic radii of the two metals. In contrast, in the Hg<jats:sup>2+<\/jats:sup>\u2010bound structure, one of the zinc ions, Zn2, was ejected, and the other zinc ion, Zn1, remained in the same site as in the 2\u2010Zn<jats:sup>2+<\/jats:sup>\u2010bound structure. Instead of the ejected zinc, a mercury ion binds between Cys 104 and Cys 181, 4.8 \u00c5 away from Zn1 and 3.9 \u00c5 away from the site where Zn2 is located in the 2\u2010Zn<jats:sup>2+<\/jats:sup>\u2010bound molecule. The perturbed binuclear metal cluster explains the inactivation of the enzyme by mercury compounds.<\/jats:p>","DOI":"10.1002\/pro.5560061225","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T05:00:24Z","timestamp":1234242024000},"page":"2671-2676","source":"Crossref","is-referenced-by-count":45,"title":["Crystal structures of the cadmium\u2010 and mercury\u2010substituted metallo\u2010\u03b2\u2010lactamase from <i>Bacteroides fragilis<\/i>"],"prefix":"10.1002","volume":"6","author":[{"given":"Nestor O.","family":"Concha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osnat","family":"Herzberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Bush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,31]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1750441"},{"key":"e_1_2_1_3_1","volume-title":"Protein crystallography","author":"Blundell TL","year":"1976"},{"key":"e_1_2_1_4_1","volume-title":"X\u2010PLOR version 3.1: A system for X\u2010ray crystallography and NMR","author":"Br\u00fcnger AT","year":"1992"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/355472a0"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.851"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1002\/j.1460-2075.1995.tb00174.x","article-title":"The 3\u2010D structure of a zinc metallo\u2010\u03b2\u2010lactamase from Bacillus cereus reveals a new type of protein fold","volume":"14","author":"Carfi A","year":"1995","journal-title":"EMBO J"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(96)00089-5"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi960976h"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1430129"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767391001071"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889887086436"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889888007903"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1107\/S002188988708662X"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-39-2-93"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.1.135"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.2116"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0980011C"},{"key":"e_1_2_1_19_1","volume-title":"Structural inorganic chemistry","author":"Wells AF","year":"1986"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.5.1155"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.5560061225","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.5560061225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T09:04:42Z","timestamp":1698483882000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.5560061225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,12]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1997,12]]}},"alternative-id":["10.1002\/pro.5560061225"],"URL":"https:\/\/doi.org\/10.1002\/pro.5560061225","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,12]]}}}