IMP-type enzymes constitute a clinically important family of metallo-β-lactamases that has grown dramatically in the past decade to its current 45 known members. Here, we report the biochemical characterization of IMP-30 in comparison to IMP-1, from which it deviates by a single E59K mutation. Kinetics, MIC assays, docking, and molecular dynamics simulations support a scenario in which Lys59 interacts with the ceftazidime R1 group, resulting in increased water access and enhanced turnover and MIC of ceftazidime.
Submitter: Peter Oelschlaeger
Submission Date: Aug. 20, 2019, 11:12 a.m.
Explanation of amino acid numbering: Mutant E23K of IMP-1 is a wild-type enzyme called IMP-30. According to the standard numbering scheme (PMID 15215079) its mutation is E59K. ND indicates not detectable (used for kinetic constants with aztreonam).
|Number of data points||180|
|Proteins||Metallo-beta-lactamase type 2|
|Assays/Quantities/Protocols||Experimental Assay: kcat ; Experimental Assay: Resistance ; Experimental Assay: MIC relative ; Experimental Assay: MIC absolute ; Experimental Assay: kcat/Km ; Experimental Assay: Km ; Derived Quantity: SD of kcat/Km ; Derived Quantity: SD of Km ; Derived Quantity: SD of kcat|
|Libraries||Activity data for IMP-1 and IMP-30 (IMP-1-E59K)|
|Percent Identity||Matching Chains||Protein||Accession||Entry Name|
|100.0||A||Metallo-beta-lactamase type 2||P52699||BLAB_SERMA|