Biochemical characterization of IMP-30, a metallo-β-lactamase with enhanced activity toward ceftazidime.
Abstract
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.
Submission Details
ID: Z5J9b5KA4
Submitter: Peter Oelschlaeger
Submission Date: Aug. 20, 2019, 11:12 a.m.
Version: 1
Publication Details
Pegg KM;Liu EM;Lacuran AE;Oelschlaeger P,Antimicrob Agents Chemother (2013) Biochemical characterization of IMP-30, a metallo-β-lactamase with enhanced activity toward ceftazidime. PMID:23836186Additional Information
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).
Study Summary
| Number of data points | 180 |
| Proteins | Metallo-beta-lactamase type 2 |
| Unique complexes | 20 |
| Assays/Quantities/Protocols | Experimental Assay: Km ; Experimental Assay: kcat/Km ; Experimental Assay: MIC absolute ; Experimental Assay: MIC relative ; Experimental Assay: Resistance ; Experimental Assay: kcat ; Derived Quantity: SD of kcat ; Derived Quantity: SD of Km ; Derived Quantity: SD of kcat/Km |
| Libraries | Activity data for IMP-1 and IMP-30 (IMP-1-E59K) |
Structure view and single mutant data analysis
Study data
| Colors: | D | E | R | H | K | S | T | N | Q | A | V | I | L | M | F | Y | W | C | G | P |
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Data Distribution
Studies with similar sequences (approximate matches)