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dc.contributor.authorLeiros, Hanna-Kirsti S.
dc.contributor.authorEdvardsen, Kine Susann Waade
dc.contributor.authorBjerga, Gro Elin Kjæreng
dc.contributor.authorSamuelsen, Ørjan
dc.date.accessioned2016-03-10T13:09:57Z
dc.date.available2016-03-10T13:09:57Z
dc.date.issued2015-02-06
dc.description.abstractDuring the last decades antimicrobial resistance has become a global health problem. Metallo-β-lactamases (MBLs) which are broad-spectrum β-lactamases that inactivate virtually all β-lactams including carbapenems, are contributing to this health problem. In this study a novel MBL variant, termed VIM-26, identified in a Klebsiella pneumoniae isolate was studied. VIM-26 belongs to the Verona integron-encoded metallo-β-lactamase (VIM) family of MBLs and is a His224Leu variant of the well-characterized VIM-1 variant. In this study, we report the kinetic parameters, minimum inhibitory concentrations and crystal structures of a recombinant VIM-26 protein, and compare them to previously published data on VIM-1, VIM-2 and VIM-7. The kinetic parameters and minimum inhibitory concentration determinations show that VIM-26, like VIM-7, has higher penicillinase activity but lower cephalosporinase activity than VIM-1 and VIM-2. The four determined VIM-26 crystal structures revealed mono- and di-zinc forms, where the Zn1 ion has distorted tetrahedral coordination geometry with an additional water molecule (W2) at a distance of 2.6–3.7 Å, which could be important during catalysis. The R2 drug binding site in VIM-26 is more open compared to VIM-2 and VIM-7 and neutrally charged due to Leu224 and Ser228. Thus, the VIM-26 drug binding properties are different from the VIM-2 (Tyr224/Arg228) and VIM-7 (His224/Arg228) structures, indicating a role of these residues in the substrate specificity.en_US
dc.descriptionAccepted manuscript version. Published version at <a href=http://doi.org/10.1111/febs.13200>http://doi.org/10.1111/febs.13200</a>.en_US
dc.identifier.citationThe FEBS Journal 2015, 282(6):1031-1042en_US
dc.identifier.cristinIDFRIDAID 1205658
dc.identifier.doi10.1111/febs.13200
dc.identifier.issn1742-4658
dc.identifier.urihttps://hdl.handle.net/10037/8855
dc.identifier.urnURN:NBN:no-uit_munin_8415
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.projectIDNorges forskningsråd: 213808en_US
dc.relation.projectIDUniversitetet i Tromsø: A32597en_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk biokjemi: 726en_US
dc.subjectVDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical biochemistry: 726en_US
dc.subjectAntibiotic resistanceen_US
dc.subjectMetallo-β-lactamaseen_US
dc.subjectKlebsiella pneumoniaeen_US
dc.subjectdrug binding siteen_US
dc.subjectminimum inhibitory concentrationsen_US
dc.titleStructural and biochemical characterization of VIM-26 shows that Leu224 has implications for the substrate specificity of VIM metallo-β-lactamasesen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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