6G9T

CRYSTAL STRUCTURE OF CMY-136 class C BETA-LACTAMASE

Summary for 6G9T

• Entry DOI: 10.2210/pdb6g9t/pdb
• Descriptor: Beta-lactamase, PHOSPHATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: class c beta-lactamase cmy-136-histag, antibiotic, dimer, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 83557.43

Authors

Zavala, A.,Retailleau, P.,Naas, T.,Iorga, B. (deposition date: 2018-04-11, release date: 2019-02-27, Last modification date: 2024-01-17)

Primary citation

Zavala, A.,Retailleau, P.,Elisee, E.,Iorga, B.I.,Naas, T.
Genetic, Biochemical, and Structural Characterization of CMY-136 beta-Lactamase, a Peculiar CMY-2 Variant.
Acs Infect Dis., 5:528-538, 2019

PubMed Abstract: With the widespread use and abuse of antibiotics for the past decades, antimicrobial resistance poses a serious threat to public health nowadays. β-Lactams are the most used antibiotics, and β-lactamases are the most widespread resistance mechanism. Class C β-lactamases, also known as cephalosporinases, usually do not hydrolyze the latest and most potent β-lactams, expanded spectrum cephalosporins and carbapenems. However, the recent emergence of extended-spectrum AmpC cephalosporinases, their resistance to inhibition by classic β-lactamase inhibitors, and the fact that they can contribute to carbapenem resistance when paired with impermeability mechanisms, means that these enzymes may still prove worrisome in the future. Here we report and characterize the CMY-136 β-lactamase, a Y221H point mutant derivative of CMY-2. CMY-136 confers an increased level of resistance to ticarcillin, cefuroxime, cefotaxime, and ceftolozane/tazobactam. It is also capable of hydrolyzing ticarcillin and cloxacillin, which act as inhibitors of CMY-2. X-ray crystallography and modeling experiments suggest that the hydrolytic profile alterations seem to be the result of an increased flexibility and altered conformation of the Ω-loop, caused by the Y221H mutation.

PubMed: 30788955
DOI: 10.1021/acsinfecdis.8b00240

Experimental method

X-RAY DIFFRACTION (1.6 Å)