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

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 ¹⁹ F NMR spectroscopy to monitor the carbamylation state of ¹⁹ F-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 ¹⁹ F-labelled OX

SUBMITTER: van Groesen E 

PROVIDER: S-EPMC6771976 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature