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.
Submitter: Shu-Ching Ou
Submission Date: March 20, 2019, 3:27 p.m.
|Structure ID||Release Date||Resolution||Structure Title|
|5ZJ1||2018-03-18T00:00:00+0000||0.96||Crystal structure of NDM-1 in complex with D-captopril derivative CYT-14|
|6C6I||2018-01-18T00:00:00+0000||1.65||Crystal structure of a chimeric NDM-1 metallo-beta-lactamase harboring the IMP-1 L3 loop|
|5ZJ2||2018-03-18T00:00:00+0000||1.1||Crystal structure of NDM-1 in complex with D-captopril|
|3PG4||2010-10-29T00:00:00+0000||2.0||The crystal structure of New Delhi Metallo-beta lactamase (NDM-1)|
|5ZJ7||2018-03-19T00:00:00+0000||0.96||Crystal structure of NDM-1 in complex with D-captopril derivative CY22|
|5ZJ8||2018-03-19T00:00:00+0000||0.96||Crystal structure of NDM-1 in complex with D-captopril derivative CY32|
|5ZGP||2018-03-10T00:00:00+0000||1.15||Crystal structure of NDM-1 at pH6.2 (Bis-Tris) in complex with hydrolyzed ampicillin|
|5ZH1||2018-03-10T00:00:00+0000||1.05||Crystal structure of NDM-1 at pH7.5 (Imidazole) with 2 molecules per asymmetric unit|
|6LJ7||2019-12-13T00:00:00+0000||1.16||Crystal structure of NDM-1 in complex with D-captopril derivative wss05010|
|3SBL||2011-06-05T00:00:00+0000||2.31||Crystal Structure of New Delhi Metal-beta-lactamase-1 from Klebsiella pneumoniae|
|Percent Identity||Matching Chains||Protein||Accession||Entry Name|
|100.0||Metallo-beta-lactamase type 2||C7C422||BLAN1_KLEPN|