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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Structure ID | Release Date | Resolution | Structure Title |
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3PG4 | 2010-10-29T00:00:00+0000 | 2.0 | The crystal structure of New Delhi Metallo-beta lactamase (NDM-1) |
3RKJ | 2011-04-18T00:00:00+0000 | 2.0 | Crystal Structure of New Delhi Metallo-Beta-Lactamase-1 from Klebsiella pnueumoniae |
3RKK | 2011-04-18T00:00:00+0000 | 2.35 | Crystal Structure of New Delhi Metallo-Beta-Lactamase-1 from Klebsiella pneumoniae |
3SBL | 2011-06-05T00:00:00+0000 | 2.31 | Crystal Structure of New Delhi Metal-beta-lactamase-1 from Klebsiella pneumoniae |
3SFP | 2011-06-13T00:00:00+0000 | 2.27 | Crystal Structure of the Mono-Zinc-boundform of New Delhi Metallo-beta-Lactamase-1 from Klebsiella pneumoniae |
3SPU | 2011-07-03T00:00:00+0000 | 2.1 | apo NDM-1 Crystal Structure |
3SRX | 2011-07-07T00:00:00+0000 | 2.5 | New Delhi Metallo-beta-Lactamase-1 Complexed with Cd |
3ZR9 | 2011-06-15T00:00:00+0000 | 1.91 | Structure of New Delhi Metallo-Beta-lactamase 1 (NDM-1) |
4EXS | 2012-04-30T00:00:00+0000 | 2.4 | Crystal structure of NDM-1 bound to L-captopril |
4EXY | 2012-05-01T00:00:00+0000 | 1.47 | Crystal structure of NDM-1 bound to ethylene glycol |
Percent Identity | Matching Chains | Protein | Accession | Entry Name |
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100.0 | Metallo-beta-lactamase type 2 | C7C422 | BLAN1_KLEPN |