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dc.contributor.authorMarcoccia, Francesca
dc.contributor.authorLeiros, Hanna-Kirsti S.
dc.contributor.authorAschi, Massimiliano
dc.contributor.authorAmicosante, Gianfranco
dc.contributor.authorPerilli, Mariagrazia
dc.date.accessioned2018-10-12T08:48:34Z
dc.date.available2018-10-12T08:48:34Z
dc.date.issued2018-01-02
dc.description.abstractBackground:<br> New Delhi Metallo-β-Lactamase (NDM-1) is one of the most recent additions to the β-lactamases family. Since its discovery in 2009, NDM-1 producing Enterobacteriaceae have disseminated globally. With few effective antibiotics against NDM-1 producers, there is an urgent need to design new drug inhibitors through the help of structural and mechanistic information available from mutagenic studies. <br>Results/Conclusions:<br> In our study we focus the attention on the non-catalytic residue Leucine 209 by changing it into a Phenylalanine. The L209F laboratory variant of NDM-1 displays a drastic reduction of catalytic efficiency (due to low kcat values) towards penicillins, cephalosporins and carbapenems. Thermofluor-based assay demonstrated that NDM-1 and L209F are stable to the temperature and the zinc content is the same in both enzymes as demonstrated by experiments with PAR in the presence of GdnHCL. Molecular Dynamics (MDs) simulations, carried out on NDM-1 and L209F both complexed and uncomplexed with Benzylpenicillin indicate that the point mutation produces a significant mechanical destabilization of the enzyme and also an increase of water content. These observations clearly show that the single mutation induces drastic changes in the enzyme properties which can be related to the observed different catalytic behavior.en_US
dc.descriptionSource at: <a href=http://doi.org/10.1371/journal.pone.0189686> http://doi.org/10.1371/journal.pone.0189686</a>en_US
dc.identifier.citationMarcoccia, F., Leiros, H.-K. S., Aschi, M., Amicosante, G. & Perilli, M. (2018). Exploring the role of L209 residue in the active site of NDM-1 a metallo-β-lactamase. PLoS ONE, 13(1), e0189686. http://doi.org/10.1371/journal.pone.0189686en_US
dc.identifier.cristinIDFRIDAID 1534988
dc.identifier.doi10.1371/journal.pone.0189686
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/13949
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLoS ONE
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Mathematics and natural science: 400::Chemistry: 440en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.titleExploring the role of L209 residue in the active site of NDM-1 a metallo-β-lactamaseen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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