Open AccessMolecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)
Author(s) -
O.A. Pemberton,
Xiujun Zhang,
Yu Chen
Publication year - 2017
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.7b00158
Subject(s) - klebsiella pneumoniae , chemistry , cefotaxime , enterobacteriaceae , antibiotics , microbiology and biotechnology , substrate (aquarium) , enzyme , serine , carbapenem , stereochemistry , biochemistry , escherichia coli , biology , gene , ecology
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.