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.
Submitter: Peter Oelschlaeger
Submission Date: Jan. 11, 2019, 4:04 p.m.
Corrections: (1) kcat for IMP-25 (mutant G169S+S196G) with cefoxotin was misreported as 30 1/s in the original publication. It should be 90 1/s. (2) kcat for IMP-25 (mutant G169S+S196G) with ampicillin was misreported as 67 1/s. It should be 47 1/s. Explanation of amino acid numbering: (1) Mutant S196G is actually a wild-type enzyme called IMP-6. According to the standard numbering scheme (PMID 15215079) , its mutation is S262G. (2) Mutant G169S+S196G is actually a wild-type enzyme called IMP-25. According to the standard numbering scheme, its mutations are G235S and S262G. Abbreviations: (1) ND indicates not detectable (used for kinetic constants with aztreonam).
|Number of data points||270|
|Proteins||Metallo-beta-lactamase type 2|
|Assays/Quantities/Protocols||Experimental Assay: Km ; Experimental Assay: kcat/Km ; Experimental Assay: kcat ; Experimental Assay: MIC absolute ; Experimental Assay: MIC relative ; Experimental Assay: Resistance ; Derived Quantity: SD of kcat ; Derived Quantity: SD of Km ; Derived Quantity: SD of kcat/Km|
|Libraries||Activity Date (Tables 1 & 2)|