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The sequence-activity relationship between metallo-?-lactamases IMP-1, IMP-6, and IMP-25 suggests an evolutionary adaptation to meropenem exposure.

ABSTRACT: Metallo-?-lactamases are important determinants of antibacterial resistance. In this study, we investigate the sequence-activity relationship between the closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more efficient enzyme across the overall spectrum of tested ?-lactam antibacterial agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation distinguishing IMP-25 from IMP-1 and IMP-6 may affect enzyme activity via Asn233.

SUBMITTER: Liu EM

PROVIDER: S-EPMC3497198 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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The sequence-activity relationship between metallo-β-lactamases IMP-1, IMP-6, and IMP-25 suggests an evolutionary adaptation to meropenem exposure.

Liu Eleanor M EM Pegg Kevin M KM Oelschlaeger Peter P

Antimicrobial agents and chemotherapy 20120924 12

Metallo-β-lactamases are important determinants of antibacterial resistance. In this study, we investigate the sequence-activity relationship between the closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more efficient enzyme across the overall spectrum of tested β-lactam antibacterial agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation distinguishing IMP-25 from IMP-1 and ...[more]

PMID: 23006757

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

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