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Article: Engineered Amp C β-lactamase as a fluorescent screening tool for class C β-lactamase inhibitors

TitleEngineered Amp C β-lactamase as a fluorescent screening tool for class C β-lactamase inhibitors
Authors
Issue Date2011
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/ac
Citation
Analytical Chemistry, 2011, v. 83 n. 6, p. 1996-2004 How to Cite?
AbstractClass C β-lactamases mediate antibiotic resistance in bacteria by efficiently hydrolyzing a broad range of β-lactam antibiotics. With their clinical significance and the lack of commercially available effective inhibitors, development of class C β-lactamase inhibitors has become one of the recent hot issues in the pharmaceutical industry. In this paper, we report the protein engineering of a fluorescent Amp C β-lactamase mutant designated as V211Cf for the in vitro screening of class C β-lactamase inhibitors. When a fluorescein (f) was incorporated at the entrance of the enzyme's active site (position 211), Amp C β-lactamase from Enterobacter cloacae P99 was tailor-made into a novel fluorescent biosensing protein that could display a fluorescence enhancement upon binding with its β-lactam substrates/inhibitors. With its catalytic activity close to the wild-type level, V211Cf can act as a "natural" fluorescent drug target for screening small binding molecules. In addition, V211Cf can allow specific detection for its active-site binding molecules and discriminate them from nondruglike molecules in the screen. Furthermore, V211Cf is amenable to a high throughput format. Taken together, V211Cf demonstrates the potential as an efficient tool for screening class C β-lactamase inhibitors and facilitates the discovery of therapeutics that can combat the clinically important class C β-lactamases. © 2011 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/168521
ISSN
2015 Impact Factor: 5.886
2015 SCImago Journal Rankings: 2.369
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTsang, MWen_US
dc.contributor.authorChan, PHen_US
dc.contributor.authorSo, PKen_US
dc.contributor.authorMa, DLen_US
dc.contributor.authorTsang, CWen_US
dc.contributor.authorWong, KYen_US
dc.contributor.authorLeung, YCen_US
dc.date.accessioned2012-10-08T03:19:58Z-
dc.date.available2012-10-08T03:19:58Z-
dc.date.issued2011en_US
dc.identifier.citationAnalytical Chemistry, 2011, v. 83 n. 6, p. 1996-2004en_US
dc.identifier.issn0003-2700en_US
dc.identifier.urihttp://hdl.handle.net/10722/168521-
dc.description.abstractClass C β-lactamases mediate antibiotic resistance in bacteria by efficiently hydrolyzing a broad range of β-lactam antibiotics. With their clinical significance and the lack of commercially available effective inhibitors, development of class C β-lactamase inhibitors has become one of the recent hot issues in the pharmaceutical industry. In this paper, we report the protein engineering of a fluorescent Amp C β-lactamase mutant designated as V211Cf for the in vitro screening of class C β-lactamase inhibitors. When a fluorescein (f) was incorporated at the entrance of the enzyme's active site (position 211), Amp C β-lactamase from Enterobacter cloacae P99 was tailor-made into a novel fluorescent biosensing protein that could display a fluorescence enhancement upon binding with its β-lactam substrates/inhibitors. With its catalytic activity close to the wild-type level, V211Cf can act as a "natural" fluorescent drug target for screening small binding molecules. In addition, V211Cf can allow specific detection for its active-site binding molecules and discriminate them from nondruglike molecules in the screen. Furthermore, V211Cf is amenable to a high throughput format. Taken together, V211Cf demonstrates the potential as an efficient tool for screening class C β-lactamase inhibitors and facilitates the discovery of therapeutics that can combat the clinically important class C β-lactamases. © 2011 American Chemical Society.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/acen_US
dc.relation.ispartofAnalytical Chemistryen_US
dc.subject.meshAnti-Bacterial Agents - Metabolism - Pharmacologyen_US
dc.subject.meshBacterial Proteins - Antagonists & Inhibitors - Chemistry - Genetics - Metabolismen_US
dc.subject.meshBiocatalysisen_US
dc.subject.meshDrug Evaluation, Preclinical - Methodsen_US
dc.subject.meshEnterobacter Cloacae - Enzymologyen_US
dc.subject.meshEnzyme Inhibitors - Metabolism - Pharmacologyen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMutationen_US
dc.subject.meshProtein Conformationen_US
dc.subject.meshProtein Engineeringen_US
dc.subject.meshSpectrometry, Fluorescenceen_US
dc.subject.meshBeta-Lactamases - Antagonists & Inhibitors - Chemistry - Genetics - Metabolismen_US
dc.subject.meshBeta-Lactams - Metabolism - Pharmacologyen_US
dc.titleEngineered Amp C β-lactamase as a fluorescent screening tool for class C β-lactamase inhibitorsen_US
dc.typeArticleen_US
dc.identifier.emailMa, DL:edmondma@hku.hken_US
dc.identifier.authorityMa, DL=rp00760en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/ac102595ren_US
dc.identifier.pmid21338058-
dc.identifier.scopuseid_2-s2.0-79954596002en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79954596002&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume83en_US
dc.identifier.issue6en_US
dc.identifier.spage1996en_US
dc.identifier.epage2004en_US
dc.identifier.isiWOS:000288182900020-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTsang, MW=36720156000en_US
dc.identifier.scopusauthoridChan, PH=36545749700en_US
dc.identifier.scopusauthoridSo, PK=14919747700en_US
dc.identifier.scopusauthoridMa, DL=7402075538en_US
dc.identifier.scopusauthoridTsang, CW=7202935952en_US
dc.identifier.scopusauthoridWong, KY=26641515400en_US
dc.identifier.scopusauthoridLeung, YC=35074432700en_US

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