Table 5.
Inhibition of Wild Type and Mutant FabIs by the Diphenyl Ether Inhibitors
| Enzyme | Compound | K1 (nM) | K2 (nM) | Inhibition pattern | MIC against S.
aureus N315 μg/mL (μM) |
|---|---|---|---|---|---|
| WT | Triclosan | 4.9 ± 0.6a | 375.1 ± 20.3a | UC with respect to NADP+. | 0.03 (0.10) |
| 5.6 ± 0.2b | 216.4 ± 7.5b | C with respect to NADPH. | |||
|
| |||||
| EPPa | 8.3 ± 0.8 | 273.1 ± 13.2 | UC with respect to NADP+. | 0.03 (0.14) | |
| CPPa | 2.0 ± 0.2 | 48.7 ± 1.6 | UC with respect to NADP+. | 0.06 (0.27) | |
|
| |||||
| Triclosanc | 8100 ± 1190 | - | UC with respect to NADPH. | 2.80 (10) | |
| A95V | EPPc | 1660 ± 50 | - | UC with respect to NADPH. | 4.40 (20) |
| CPPc | 6150 ± 160 | - | UC with respect to NADPH. | 8.80 (40) | |
|
| |||||
| Triclosand | 35 ± 18 | 473 ± 196 | NC with respect to NADPH. | 2.80 (10) | |
| I193S | EPPd | 41 ± 5 | 783 ± 281 | NC with respect to NADPH. | 8.80 (40) |
| CPPd | 52 ± 2 | 690 ± 320 | NC with respect to NADPH. | 17.60 (80) | |
|
| |||||
| Triclosanc | 210 ± 20 | - | UC with respect to NADPH. | 0.70 (2.5) | |
| F204S | EPPd | 160 ± 60 | 300 ± 110 | NC with respect to NADPH. | 2.20 (10) |
| CPPc | 570 ± 30 | - | UC with respect to NADPH. | 8.80 (40) | |
a
NADP+ was varied;
b
NADPH was varied;
c
Uncompetitive. Kii has been listed under K1. Enzyme concentration was 200 nM;
d
noncompetitive inhibition. Kii has been listed under K1, and Kis has been listed under K2. Kii and Kis were defined by Cleland previously (33).