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)|
|Structure ID||Release Date||Resolution||Structure Title|
|6JED||2019-08-07||1.57||Crystal structure of IMP-1 metallo-beta-lactamase in a complex with MCR|
|5Y5B||2018-08-08||1.7||Crystal Structure Of IMP-1 Metallo-beta-lactamase|
|4C1G||2014-08-27||1.71||Crystal structure of the metallo-beta-lactamase IMP-1 with D-captopril|
|5EV6||2016-06-01||1.98||Crystal structure of the native, di-zinc metallo-beta-lactamase IMP-1|
|1DD6||2000-11-08||2.0||IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR|
|5HH4||2017-01-18||2.0||Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor|
|4C1F||2014-08-27||2.01||Crystal structure of the metallo-beta-lactamase IMP-1 with L-captopril|
|1WUO||2005-03-29||2.01||Crystal structure of metallo-beta-lactamase IMP-1 mutant (D81A)|
|5EV8||2016-06-01||2.3||Crystal structure of the metallo-beta-lactamase IMP-1 in complex with the bisthiazolidine inhibitor D-CS319|
|5EWA||2016-06-01||2.3||Crystal structure of the metallo-beta-lactamase IMP-1 in complex with the bisthiazolidine inhibitor L-VC26|
|1VGN||2005-06-21||2.63||Structure-based design of the irreversible inhibitors to metallo--lactamase (IMP-1)|
|1WUP||2005-03-29||3.0||Crystal structure of metallo-beta-lactamase IMP-1 mutant (D81E)|
|Percent Identity||Matching Chains||Protein||Accession||Entry Name|
|100.0||Metallo-beta-lactamase type 2||P52699||BLAB_SERMA|