Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/6548
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dc.contributor.authorLahiri SDen_us
dc.contributor.authorMangani Sen_us
dc.contributor.authorJahić Hen_us
dc.contributor.authorBenvenuti Men_us
dc.contributor.authorDurand-Reville TFen_us
dc.contributor.authorDe Luca Fen_us
dc.contributor.authorEhmann DEen_us
dc.contributor.authorRossolini GMen_us
dc.contributor.authorAlm RAen_us
dc.contributor.authorDocquier JDen_us
dc.date.accessioned2021-03-30T16:04:06Z-
dc.date.available2021-03-30T16:04:06Z-
dc.date.issued2015-
dc.identifier.issn1554-8929en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12779/6548-
dc.description104709en_US
dc.description.abstractThe Class D (or OXA-type) beta-lactamases have expanded to be the most diverse group of serine beta-lactamases with a highly heterogeneous beta-lactam hydrolysis profile and are typically resistant to marketed beta-lactamase inhibitors. Class D enzymes are increasingly found in multidrug resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and various species of the Enterobacteriaceae and are posing a serious threat to the clinical utility of beta-lactams including the carbapenems, which are typically reserved as the drugs of last resort. Avibactam, a novel non-beta-lactam beta-lactamase inhibitor, not only inhibits all class A and class C beta-lactamases but also has the promise of inhibition of certain OXA enzymes, thus extending the antibacterial activity of the beta-lactam used in combination to the organisms that produce these enzymes. X-ray structures of OXA-24 and OXA-48 in complex with avibactam revealed the binding mode of this inhibitor in this diverse class of enzymes and provides a rationale for selective inhibition of OXA-48 members. Additionally, various subunits of the OXA-48 structure in the asymmetric unit provide snapshots of different states of the inhibited enzyme. Overall, these data provide the first structural evidence of the exceptionally slow reversibility observed with avibactam in class D beta-lactamases. Mechanisms for acylation and deacylation of avibactam by class D enzymes are proposed, and the likely extent of inhibition of class D beta-lactamases by avibactam is discussed.en_US
dc.language.isoenen_US
dc.relationNoneen_US
dc.relation.ispartofACS CHEMICAL BIOLOGYen_US
dc.titleMolecular Basis of Selective Inhibition and Slow Reversibility of Avibactam against Class D Carbapenemases: A Structure-Guided Study of OXA-24 and OXA-48.en_US
dc.typeArticleen_US
dc.identifier.doi10.1021/cb500703pen_US
dc.identifier.pmid25406838en_US
dc.identifier.scopus2-s2.0-84923338309en_US
dc.identifier.isi000349942700029en_US
dc.relation.volume10en_US
dc.relation.issue2en_US
dc.description.firstpage591en_US
dc.description.lastpage600en_US
dc.description.thirdmissionNot applicableen_US
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeArticle-
item.fulltextNo Fulltext-
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