Work

Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)

Year: 2017

Type: article

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.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/acs.jmedchem.7b00158

Authors: Orville A. Pemberton, Xiujun Zhang, Yu Chen

Institution: University of South Florida

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases

Awards: G2831496221, Evolution and inhibition of beta-lactamase activity in antibiotic resistance