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CRYSTAL STRUCTURE OF CMY-136 class C BETA-LACTAMASECRYSTAL STRUCTURE OF CMY-136 class C BETA-LACTAMASE
Structural highlights
Publication Abstract from PubMedWith the widespread use and abuse of antibiotics for the past decades, antimicrobial resistance poses a serious threat to public health nowadays. beta-Lactams are the most used antibiotics, and beta-lactamases the most widespread resistance mechanism. Class C beta-lactamases, also known as cephalosporinases, usually do not hydrolyse the latest and most potent beta-lactams, expanded spectrum cephalosporins and carbapenems. However, the recent emergence of extended-spectrum AmpC cephalosporinases, their resistance to inhibition by classic beta-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 beta-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 hydrolysing ticarcillin and cloxacillin, which act as inhibitors of CMY-2. X-ray crystallography and modelling experiments suggest that the hydrolytic profile alterations seem to be the result of an increased flexibility and altered conformation of the Omega-loop, caused by the Y221H mutation. Genetic, biochemical and structural characterization of CMY-136 beta-lactamase, a peculiar CMY-2 variant.,Zavala A, Retailleau P, Elisee E, Iorga BI, Naas T ACS Infect Dis. 2019 Feb 21. doi: 10.1021/acsinfecdis.8b00240. PMID:30788955[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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