TABLE 4.
Zinc dependence of metallo-β-lactamase-catalyzed hydrolysis of β-lactam antibioticsa
| Substrate | Metallo-β-lactamase zinc dissociation constantb (Kd,Zn2) |
|||||
|---|---|---|---|---|---|---|
| NDM-1 | NDM-4 | NDM-6 | VIM-2 | IMP-7 | AIM-1 | |
| Ampicillin | 0.91 ± 0.07 | 0.15 ± 0.02 | 0.23 ± 0.02 | 0.45 ± 0.05 | 0.24 ± 0.04 | 0.19 ± 0.05 |
| Cefotaxime | 1.4 ± 0.3 | 0.17 ± 0.03 | 0.24 ± 0.02 | 0.21 ± 0.03 | 0.80 ± 0.4 | 0.33 ± 0.07 |
| Meropenem | 3.2 ± 0.5 | 0.3 ± 0.06 | 0.64 ± 0.08 | 0.63 ± 0.1 | 0.46 ± 0.08 | 0.52 ± 0.08 |
| Imipenem | 0.4 ± 0.04 | 0.06 ± 0.007 | 0.14 ± 0.01 | 0.34 ± 0.09 | 0.95 ± 0.3 | 0.59 ± 0.07 |
| Ertapenem | 2.8 ± 1 | 4.3 ± 2.6 | 2.0 ± 0.3 | 2.3 ± 1 | 2.0 ± 0.4 | 0.95 ± 0.2 |
| Doripenem | 1.1 ± 0.1 | 0.18 ± 0.02 | 0.14 ± 0.08 | 0.38 ± 0.03 | 0.082 ± 0.01 | 0.90 ± 0.1 |
a
Reactions were carried out with enzyme (4 to 10 nM) in Chelex-treated HEPES-NaOH, pH 7.5 (50 mM), supplemented with AMA (100 nM).
b
All constants are reported in micromolar (μM).