{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T10:48:43Z","timestamp":1758278923583},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,6,1]]},"abstract":"<jats:p>The OHIO-1 beta-lactamase does not normally hydrolyse oxyimino-beta-lactam substrates like cefotaxime, ceftriaxone, ceftazidime or aztreonam. We were able to select spontaneous mutants of an OHIO-1-bearing strain of Escherichia coli using the antibiotic substrates listed above by enrichment methods of frequencies of 10(-8)-10(-10) for all antibiotics except ceftazidime (frequency less than 10(-10)). Most mutants with increased resistance to the other beta-lactams were also more resistant to ceftazidime. Mutations identified by DNA sequencing included a Gly238----Ser238 substitution identical with the SHV-2 mutation previously described, cysteine and valine substitutions at the identical site, and a Gly242----Cys242 substitution. The Cys238 and Cys242 mutant enzymes had less affinity for aztreonam than had the other mutant enzymes. Hydrolysis of cefotaxime, but not cephaloridine, by the cysteine-substituted enzymes was inhibited by p-chloromercuribenzoate. The mutant enzymes had, in general, greater affinity for the mechanism-based inhibitors sulbactam, clavulanic acid and tazobactam. These results suggest two non-mutually exclusive hypotheses for the structural role of substitutions in this area of the enzyme. Either potential hydrogen-bond donors, such as serine and cysteine, interact directly with the beta-lactam molecules, or the steric bulk of these substitutions distorts the beta-pleated sheet such that the beta-lactam is held in a position favourable for stable binding and catalysis. Finally, our data raise questions about a strategy relying on oligonucleotide-probe technology to detect such mutations, because of the variety of substitutions that give rise to similar phenotypes.<\/jats:p>","DOI":"10.1042\/bj2840411","type":"journal-article","created":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T21:20:57Z","timestamp":1439500857000},"page":"411-415","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mutations altering substrate specificity in OHIO-1, and SHV-1 family <i>\u03b2<\/i>-lactamase"],"prefix":"10.1042","volume":"284","author":[{"given":"D M","family":"Shlaes","sequence":"first","affiliation":[{"name":"Medical and Research Services, Veterans Affairs Medical Center, Division of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Currie-McCumber","sequence":"additional","affiliation":[{"name":"Medical and Research Services, Veterans Affairs Medical Center, Division of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/284\/2\/411\/606996\/bj2840411.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/284\/2\/411\/606996\/bj2840411.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T21:56:11Z","timestamp":1637704571000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/284\/2\/411\/28109\/Mutations-altering-substrate-specificity-in-OHIO-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,6,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1992,6,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj2840411","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,6,1]]}}}