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    19F NMR Monitoring of Reversible Protein Post‐Translational Modifications: Class D β‐Lactamase Carbamylation and Inhibition

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    Date
    2019
    Author
    van Groesen, Emma
    Lohans, Christopher T.
    Brem, Jürgen
    Aertker, Kristina M.
    Claridge, Timothy D. W.
    Schofield, Christopher J.
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    Abstract
    Bacterial production of β‐lactamases with carbapenemase activity is a global health threat. The active sites of class D carbapenemases such as OXA‐48, which is of major clinical importance, uniquely contain a carbamylated lysine residue which is essential for catalysis. Although there is significant interest in characterizing this post‐translational modification, and it is a promising inhibition target, protein carbamylation is challenging to monitor in solution. We report the use of 19F NMR spectroscopy to monitor the carbamylation state of 19F‐labelled OXA‐48. This method was used to investigate the interactions of OXA‐48 with clinically used serine β‐lactamase inhibitors, including avibactam and vaborbactam. Crystallographic studies on 19F‐labelled OXA‐48 provide a structural rationale for the sensitivity of the 19F label to active site interactions. The overall results demonstrate the use of 19F NMR to monitor reversible covalent post‐translational modifications.
    URI for this record
    http://hdl.handle.net/1974/27460
    External DOI
    https://doi.org/10.1002/chem.201902529
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    • Department of Biomedical and Molecular Sciences Faculty Publications
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