Meropenem and chromacef intermediates observed in IMP-25 metallo-β-lactamase-catalyzed hydrolysis

Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2015-07, Vol.59 (7), p.4326-4330
Main Authors: Oelschlaeger, Peter, Aitha, Mahesh, Yang, Hao, Kang, Joon S, Zhang, Antonia L, Liu, Eleanor M, Buynak, John D, Crowder, Michael W
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents
Anti-Bacterial Agents - metabolism
beta-Lactamases
beta-Lactamases - genetics
beta-Lactamases - metabolism
Catalysis
Catalytic Domain
Cephalosporins
Cephalosporins - metabolism
Hydrolysis
Kinetics
Mechanisms of Resistance
Thienamycins
Thienamycins - metabolism
Zinc - metabolism
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Summary:Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of an intermediate has not been shown conclusively in imipenemase (IMP) enzymes to date. Here, we provide evidence that intermediates are formed during the hydrolysis of meropenem and chromacef catalyzed by the variant IMP-25 and, to a lesser degree, IMP-1.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.04409-14