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:
-
- Univ. of South Florida, Tampa, FL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH)
- OSTI Identifier:
- 1368248
- Grant/Contract Number:
- AI103158
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Journal of Medicinal Chemistry
- Additional Journal Information:
- Journal Volume: 60; Journal Issue: 8; Journal ID: ISSN 0022-2623
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Antimicrobial agents; Peptides and proteins; Monomers; Chemical structure; Conformation
Citation Formats
Pemberton, Orville A., Zhang, Xiujun, and Chen, Yu. Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2). United States: N. p., 2017.
Web. doi:10.1021/acs.jmedchem.7b00158.
Pemberton, Orville A., Zhang, Xiujun, & Chen, Yu. Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2). United States. https://doi.org/10.1021/acs.jmedchem.7b00158
Pemberton, Orville A., Zhang, Xiujun, and Chen, Yu. 2017.
"Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)". United States. https://doi.org/10.1021/acs.jmedchem.7b00158. https://www.osti.gov/servlets/purl/1368248.
@article{osti_1368248,
title = {Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)},
author = {Pemberton, Orville A. and Zhang, Xiujun and Chen, Yu},
abstractNote = {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.},
doi = {10.1021/acs.jmedchem.7b00158},
url = {https://www.osti.gov/biblio/1368248},
journal = {Journal of Medicinal Chemistry},
issn = {0022-2623},
number = 8,
volume = 60,
place = {United States},
year = {Mon Apr 17 00:00:00 EDT 2017},
month = {Mon Apr 17 00:00:00 EDT 2017}
}
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