New Delhi metallo-β-lactamase 1 (NDM-1) is a subclass B1 metallo-β-lactamase that exhibits a broad spectrum of activity against β-lactam antibiotics. Here we report the kinetic study of 6 Q119X variants obtained by site-directed mutagenesis of NDM-1. All Q119X variants were able to hydrolyze carbapenems, penicillins and first-, second-, third-, and fourth-generation cephalosporins very efficiently. In particular, Q119E, Q119Y, Q119V, and Q119K mutants showed improvements in kcat/Km values for penicillins, compared with NDM-1. The catalytic efficiencies of the Q119K variant for benzylpenicillin and carbenicillin were about 65- and 70-fold higher, respectively, than those of NDM-1. The Q119K and Q119Y enzymes had kcat/Km values for ceftazidime about 25- and 89-fold higher, respectively, than that of NDM-1.
ID: CWvASvaZ3
Submitter: Shu-Ching Ou
Submission Date: March 20, 2019, 3:27 p.m.
Version: 1
Number of data points | 299 |
Proteins | Metallo-beta-lactamase type 2 |
Unique complexes | 117 |
Assays/Quantities/Protocols | Experimental Assay: kcat/Km ; Experimental Assay: Km ; Experimental Assay: kcat ; Experimental Assay: MIC |
Libraries | Variants for NDM-1_Substrate |
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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Percent Identity | Matching Chains | Protein | Accession | Entry Name |
---|---|---|---|---|
100.0 | Metallo-beta-lactamase type 2 | C7C422 | BLAN1_KLEPN |