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

Document Type

Article

Publication Date

2017

Digital Object Identifier (DOI)

https://doi.org/10.1021/acs.jmedchem.7b00158

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.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Journal of Medicinal Chemistry, v. 60, issue 8, p. 3525-3530

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