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Cefdinir binding to a class-A β-lactamase revealed by serial cryo-crystallography

Gore, G.; Prester, A.; Bartels, K.; Stetten, D. v.; Schulz, E. C.

2025-12-13 biophysics
10.64898/2025.12.11.693660 bioRxiv
Show abstract

One of the most common resistance mechanisms against antibiotics employed by Gram-negative bacteria involves the production of {beta}-lactamases, resulting in rapid hydrolysis of the antibiotic. Extensive use of the early generation cephalosporins led to the rise of extended-spectrum {beta}-lactamases (ESBLs) like CTX-Ms. Cefdinir is an extended-spectrum third-generation cephalosporin administered since the late 90s; despite this, there is no reported 3D-structure of the antibiotic bound to any {beta}-lactamase or Penicillin-Binding-Protein (PBP) in the PDB. Here we report the X-ray crystallographic structure of Cefdinir-bound CTX-M-14 E166A mutant obtained via serial cryo-crystallography (cryo-SSX). SynopsisSerial cryo-crystallography reveals the structure of the extended spectrum {beta}-lactamase CTX-M-14, in complex with the third-generation cephalosporin antibiotic Cefdinir.

Published in Acta Crystallographica Section D Structural Biology (predicted rank #1) · training set

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