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Publication Abstract from PubMed

Bacterial production of beta-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 beta- 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.

19F-NMR Monitoring of Reversible Protein Post-Translational Modifications: Class D beta-Lactamase Carbamylation and Inhibition.,van Groesen E, Lohans CT, Brem J, Aertker KM, Claridge TD, Schofield C Chemistry. 2019 Jul 16. doi: 10.1002/chem.201902529. PMID:31310409^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.