Comparison of verona integron-borne metallo-β-lactamase (VIM) variants reveals differences in stability and inhibition profiles

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dc.authorid0000-0002-7757-6812en_US
dc.contributor.authorMakena, Anne
dc.contributor.authorDüzgün, Azer Özad
dc.contributor.authorBrem, Jurgen
dc.contributor.authorMcDonough, Michael A.
dc.contributor.authorRydzik, Anna M.
dc.contributor.authorAbboud, Martine I.
dc.contributor.authorÇopur Çiçek, Ayşegül
dc.contributor.authorSandallı, Cemal
dc.contributor.authorSchofield, Christopher J.
dc.date.accessioned2020-11-10T13:09:13Z
dc.date.available2020-11-10T13:09:13Z
dc.date.issued2015
dc.departmentAÇÜ, Sağlık Bilimleri Fakültesien_US
dc.description.abstractMetallo-beta-lactamases (MBLs) are of increasing clinical significance; the development of clinically useful MBL inhibitors is challenged by the rapid evolution of variant MBLs. The Verona integron-borne metallo-beta-lactamase (VIM) enzymes are among the most widely distributed MBLs, with > 40 VIM variants having been reported. We report on the crystallographic analysis of VIM-5 and comparison of biochemical and biophysical properties of VIM-1, VIM-2, VIM-4, VIM-5, and VIM-38. Recombinant VIM variants were produced and purified, and their secondary structure and thermal stabilities were investigated by circular dichroism analyses. Steady-state kinetic analyses with a representative panel of beta-lactam substrates were carried out to compare the catalytic efficiencies of the VIM variants. Furthermore, a set of metalloenzyme inhibitors were screened to compare their effects on the different VIM variants. The results reveal only small variations in the kinetic parameters of the VIM variants but substantial differences in their thermal stabilities and inhibition profiles. Overall, these results support the proposal that protein stability may be a factor in MBL evolution and highlight the importance of screening MBL variants during inhibitor development programs.
dc.description.sponsorshipThe Rhodes Trust provided funding to Anne Makena. Scientific and Technology Council of Turkey provided funding to Cemal Sandalli. Recep Tayyip Erdogan Universitesi Research Fund provided funding to Aysegul Saral, Aysegul C. Cicek, and Cemal Sandalli under grant number BAP-2013.102.03.13. Medical Research Council provided funding to Jurgen Brem, Michael A. McDonough, Anna M. Rydzik, and Christopher J. Schofield under grant number MR/L007665/1. Medical Research Council/Canadian Grant provided funding to Jurgen Brem, Michael A. McDonough, Anna M. Rydzik, and Christopher J. Schofield under grant number G1100135. Biochemical Society Krebs Memorial Award provided funding to Martine I. Abboud.en_US
dc.identifier.citationMakena, A., Düzgün, A. Ö., Brem, J., McDonough, M. A., Rydzik, A. M., Abboud, M. I., ... & Schofield, C. J. (2016). Comparison of Verona integron-borne metallo-β-lactamase (VIM) variants reveals differences in stability and inhibition profiles. Antimicrobial Agents and Chemotherapy, 60(3), 1377-1384.en_US
dc.identifier.doi10.1128/AAC.01768-15
dc.identifier.endpage1384en_US
dc.identifier.issue3en_US
dc.identifier.scopusqualityQ1
dc.identifier.startpage1377en_US
dc.identifier.urihttps://hdl.handle.net/11494/2441
dc.identifier.volume60en_US
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorSaral, Ayşegül
dc.language.isoenen_US
dc.publisherAmer Soc Microbiologyen_US
dc.relation.ispartofAntimicrobial Agents and Chemotherapy
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keywords Available]en_US
dc.titleComparison of verona integron-borne metallo-β-lactamase (VIM) variants reveals differences in stability and inhibition profilesen_US
dc.title.alternativeComparison of verona integron-borne metallo- beta-lactamase (VIM) variants reveals differences in stability and inhibition profilesen_US
dc.typeArticle

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