7UON

CTX-M-14 Y105W mutant

Summary for 7UON

• Entry DOI: 10.2210/pdb7uon/pdb
• Descriptor: Beta-lactamase, PHOSPHATE ION (3 entities in total)
• Functional Keywords: beta-lactamase, antimicrobial protein
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 28118.55

Authors

Judge, A.,Hu, L.,Sankaran, B.,Van Riper, J.,Prasad, B.V.V.,Palzkill, T. (deposition date: 2022-04-13, release date: 2023-01-25, Last modification date: 2023-10-25)

Primary citation

Judge, A.,Hu, L.,Sankaran, B.,Van Riper, J.,Venkataram Prasad, B.V.,Palzkill, T.
Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M beta-lactamase.
Commun Biol, 6:35-35, 2023

PubMed Abstract: CTX-M β-lactamases are prevalent antibiotic resistance enzymes and are notable for their ability to rapidly hydrolyze the extended-spectrum cephalosporin, cefotaxime. We hypothesized that the active site sequence requirements of CTX-M-mediated hydrolysis differ between classes of β-lactam antibiotics. Accordingly, we use codon randomization, antibiotic selection, and deep sequencing to determine the CTX-M active-site residues required for hydrolysis of cefotaxime and the penicillin, ampicillin. The study reveals positions required for hydrolysis of all β-lactams, as well as residues controlling substrate specificity. Further, CTX-M enzymes poorly hydrolyze the extended-spectrum cephalosporin, ceftazidime. We further show that the sequence requirements for ceftazidime hydrolysis follow those of cefotaxime, with the exception that key active-site omega loop residues are not required, and may be detrimental, for ceftazidime hydrolysis. These results provide insights into cephalosporin hydrolysis and demonstrate that changes to the active-site omega loop are likely required for the evolution of CTX-M-mediated ceftazidime resistance.

PubMed: 36635385
DOI: 10.1038/s42003-023-04422-z

Experimental method

X-RAY DIFFRACTION (1.35 Å)