{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:17:42Z","timestamp":1791670662536,"version":"4.3.4"},"reference-count":76,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,4]],"date-time":"2008-06-04T00:00:00Z","timestamp":1212537600000},"content-version":"vor","delay-in-days":155,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioinorganic Chemistry and Applications"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>Class B <jats:italic>\u03b2<\/jats:italic>\u2010lactamases or metallo\u2010<jats:italic>\u03b2<\/jats:italic>\u2010lactamases (MBLs) require zinc ions to catalyse the hydrolysis of <jats:italic>\u03b2<\/jats:italic>\u2010lactam antibiotics such as penicillins, cephalosporins, carbapenems,  and cephamycins. There are no clinically useful inhibitors against MBLs which are responsible for the resistance of some bacteria to antibiotics. There are two metal\u2010ion binding sites that have different zinc ligands but the exact roles of the metal\u2010ion remain controversial,  and distinguishing between their relative importance is complex. The metal\u2010ion can act as a Lewis acid by co\u2010ordination to the <jats:italic>\u03b2<\/jats:italic>\u2010lactam carbonyl oxygen to facilitate nucleophilic attack and stabilise the negative charge developed on this oxygen in the tetrahedral intermediate anion. The metal\u2010ion also lowers the pKa of the directly co\u2010ordinated water molecule so that the metal\u2010bound hydroxide ion is a better nucleophile than water and is used to attack the <jats:italic>\u03b2<\/jats:italic>\u2010lactam carbonyl carbon.  An intrinsic property of binuclear metallo hydrolytic enzymes that depend on a metal\u2010bound water both as the attacking nucleophile and as a ligand for the second metal\u2010ion is that this water molecule, which is consumed during hydrolysis of the substrate, has to be replaced to maintain the catalytic cycle. With MBL this is reflected in some unusual kinetic profiles.\n\n\n\n<\/jats:p>","DOI":"10.1155\/2008\/576297","type":"journal-article","created":{"date-parts":[[2008,6,11]],"date-time":"2008-06-11T06:47:53Z","timestamp":1213166873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["The Mechanisms of Catalysis by Metallo <i>\u03b2<\/i>\u2010Lactamases"],"prefix":"10.1155","volume":"2008","author":[{"given":"Michael I.","family":"Page","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Badarau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,4]]},"reference":[{"key":"e_1_2_4_1_2","doi-asserted-by":"crossref","unstructured":"PageM. I. PageM. I. 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