New Delhi metallo- beta-lactamase 1 (NDM-1) is a subclass B1 metallo-beta -
lactamase that exhibits a broad spectrum of activity against beta -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
