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:23836186
Additional 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).

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
6JED 2019-02-05T00:00:00+0000 1.57 Crystal structure of IMP-1 metallo-beta-lactamase in a complex with MCR
5Y5B 2017-08-08T00:00:00+0000 1.7 Crystal Structure Of IMP-1 Metallo-beta-lactamase
1WUO 2004-12-08T00:00:00+0000 2.01 Crystal structure of metallo-beta-lactamase IMP-1 mutant (D81A)
1WUP 2004-12-08T00:00:00+0000 3.0 Crystal structure of metallo-beta-lactamase IMP-1 mutant (D81E)
5HH4 2016-01-09T00:00:00+0000 2.0 Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor
1DD6 1999-11-08T00:00:00+0000 2.0 IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR
4C1F 2013-08-12T00:00:00+0000 2.01 Crystal structure of the metallo-beta-lactamase IMP-1 with L-captopril
6ZYR 2020-08-02T00:00:00+0000 1.87 Structure of IMP-1 with 2-Mercaptomethyl-thiazolidine L-anti-1b
6ZYS 2020-08-02T00:00:00+0000 1.87 Structure of IMP-1 with 2-Mercaptomethyl-thiazolidine D-syn-1b
6JKA 2019-02-28T00:00:00+0000 2.01 Crystal structure of metallo-beta-lactamse, IMP-1, in complex with a thiazole-bearing inhibitor

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 A Metallo-beta-lactamase type 2 P52699 BLAB_SERMA