Structural and Biochemical Features of OXA-517: a Carbapenem and Expanded-Spectrum Cephalosporin Hydrolyzing OXA-48 Variant
Laura Dabos, J.E. Raczynska, Pierre Bogaerts, Agustín Jacinto Zavala, Delphine Girlich, Rémy A. Bonnin, Laurent Dortet, Aurélie Peyrat, Pascal Retailleau, Bogdan I. Iorga, Mariusz Jaskólski, Y. Glupczynski, Thierry Naas
Abstract
operon. The crystal structure of OXA-517, determined to 1.86 Å resolution, revealed an expanded active site compared to that of OXA-48, which allows for accommodation of the bulky ceftazidime substrate. Our work illustrates the remarkable propensity of OXA-48-like carbapenemases to evolve through mutation/deletion in the β5-β6 loop to extend its hydrolysis profile to encompass most β-lactam substrates.
Topics & Concepts
OperonPlasmidCarbapenemCephalosporinGeneMutationHydrolysisBiologyHydrolaseCeftazidimeMutantEnzymeMicrobiologyChemistryGeneticsStereochemistryBiochemistryPseudomonas aeruginosaBacteriaAntibioticsAntibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyInfections and bacterial resistance