Abstract
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 IMP-6 may affect enzyme activity via Asn233.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Biological / genetics*
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Adaptation, Biological / physiology
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Amino Acid Sequence
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Anti-Bacterial Agents / pharmacology*
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Bacterial Proteins / chemistry
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Bacterial Proteins / drug effects
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Bacterial Proteins / genetics*
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Biological Evolution
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Drug Resistance, Bacterial / genetics*
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Kinetics
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Meropenem
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Sequence Data
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Mutation / genetics
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Thienamycins / pharmacology*
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beta-Lactamases / drug effects*
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beta-Lactamases / genetics*
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beta-Lactams / pharmacology
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Thienamycins
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beta-Lactams
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beta-lactamase IMP-1
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beta-Lactamases
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beta-lactamase IMP-25, Pseumonas aeruginosa
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Meropenem