title: Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2).
abstract: Carbapenem-resistant Enterobacteriaceae are resistant to most β-lactam antibiotics due to the production of the Klebsiella pneumoniae carbapenemase (KPC-2) class A β-lactamase. Here, we present the first product complex crystal structures of KPC-2 with β-lactam antibiotics containing hydrolyzed cefotaxime and faropenem. They provide experimental insights into substrate recognition by KPC-2 and its unique cephalosporinase/carbapenemase activity. These structures also represent the first product complexes for a wild-type serine β-lactamase, elucidating the product release mechanism of these enzymes in general.
authors.affiliation: Department of Molecular Medicine, University of South Florida , 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, United States.
authors.forename: Orville A
authors.initials: OA
authors.lastname: Pemberton
authors.affiliation: Department of Molecular Medicine, University of South Florida , 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, United States.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Medicine, University of South Florida , 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, United States.
authors.forename: Yu
authors.identifier: 0000-0002-5115-3600
authors.initials: Y
authors.lastname: Chen
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase