6RJ7

Crystal structure of the 19F labelled OXA-48

Summary for 6RJ7

• Entry DOI: 10.2210/pdb6rj7/pdb
• Descriptor: Beta-lactamase, CHLORIDE ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: beta lactmase, antibiotic resistance, 19f labelling, antimicrobial protein
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 57226.15

Authors

Brem, J.,Lohans, C.,Schofield, C. (deposition date: 2019-04-26, release date: 2019-07-31, Last modification date: 2024-01-24)

Primary citation

van Groesen, E.,Lohans, C.T.,Brem, J.,Aertker, K.M.J.,Claridge, T.D.W.,Schofield, C.J.
19F NMR Monitoring of Reversible Protein Post-Translational Modifications: Class D beta-Lactamase Carbamylation and Inhibition.
Chemistry, 25:11837-11841, 2019

PubMed 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 F NMR spectroscopy to monitor the carbamylation state of 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 F-labelled OXA-48 provide a structural rationale for the sensitivity of the F label to active site interactions. The overall results demonstrate the use of F NMR to monitor reversible covalent post-translational modifications.

PubMed: 31310409
DOI: 10.1002/chem.201902529

Experimental method

X-RAY DIFFRACTION (1.73002235119 Å)