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dc.contributor.authorWieske, Lianne H. E.
dc.contributor.authorBogaerts, Jonathan
dc.contributor.authorLeding, Albin A. M.
dc.contributor.authorWilcox, Scott
dc.contributor.authorRasmussen, Anna Andersson
dc.contributor.authorLeszczak, Kinga
dc.contributor.authorTurunen, Lotta
dc.contributor.authorHerrebout, Wouter A.
dc.contributor.authorHubert, Madlen
dc.contributor.authorBayer, Annette
dc.contributor.authorErdelyi, Mate
dc.date.accessioned2022-06-16T09:08:41Z
dc.date.available2022-06-16T09:08:41Z
dc.date.issued2022-01-28
dc.description.abstractCarbapenem resistance caused by metallo-β-lactamases is a serious global challenge that, if not tackled efficiently, is expected to lead to millions of deaths in the coming decades. Verona-integron encoded metallo-β-lactamase 2 (VIM-2) is a bacterial enzyme that has been reported from multidrug-resistant nosocomial isolates of Pseudomonas aeruginosa and other Gram-negative pathogens. As it hydrolyzes most β-lactams efficiently, including carbapenems, it is a major threat to current antimicrobial chemotherapies. So far, there is no clinically applicable inhibitor for this enzyme. In this work, the backbone NMR resonance assignment of VIM-2 is disclosed, opening up NMR investigations of this clinically important enzyme and its potential inhibitors for solutions, enabling a rational improvement of inhibitor candidates. Making use of the assignment, we identified the active enantiomer of a VIM-2 inhibitor candidate as well as its possible binding site and Kd, utilizing NMR chemical shift titration experiments.en_US
dc.identifier.citationWieske, Bogaerts, Leding, Wilcox, Rasmussen, Leszczak K, Turunen L, Herrebout, Hubert, Bayer A, Erdelyi M. NMR Backbone Assignment of VIM-2 and Identification of the Active Enantiomer of a Potential Inhibitor. ACS Medicinal Chemistry Letters. 2022;13(2):257-261en_US
dc.identifier.cristinIDFRIDAID 1994883
dc.identifier.doi10.1021/acsmedchemlett.1c00635
dc.identifier.issn1948-5875
dc.identifier.urihttps://hdl.handle.net/10037/25490
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.journalACS Medicinal Chemistry Letters
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.titleNMR Backbone Assignment of VIM-2 and Identification of the Active Enantiomer of a Potential Inhibitoren_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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