Table 5.
Interaction of polycyclic aromatic inhibitors with human P450 1B1
| acetylenic inhibitors | PAH binding to P450 1B1 | PAH inhibitors | PAH binding to P450 1B1 | ||
|---|---|---|---|---|---|
| Kd, μM | Bmax (%) | Kd, μM | Bmax (%) | ||
| 1EP | 1.9± 0.1 | 74 ± 1 | B[a]A | 2.0 ± 0.1 | 46 ± 1 |
| 2EP | 2.1 ± 0.3 | 69 ± 3 | chrysene | 4.3 ± 0.6 | 84 ± 6 |
| 4EP | 0.9 ± 0.1 | 67 ± 3 | 5MeCh | 1.9 ± 0.3 | 83 ± 5 |
| 1VP | 2.0 ± 0.2 | 65 ± 2 | DMBA | 3.1 ± 0.3 | 62 ± 1 |
| 1PP | 1.9 ± 0.4 | 69 ± 1 | B[a]P | 1.0 ± 0.2 | 77 ± 4 |
| 2EPh | 4.7 ± 0.6 | 62 ± 4 | B[e]P | 6.3 ± 0.8 | 100 ± 6 |
| 3EPh | 9.2 ± 3.0 | 108 ± 22 | DB[a,j]Ac | 1.6 ± 0.3 | 62 ± 4 |
| 9EPh | 1.6 ± 0.3 | 52 ± 3 | 3MC | 4.8 ± 0.5 | 105 ± 6 |
| 2PPh | 4.6 ± 0.6 | 77 ± 5 | FA | 1.1 ± 0.1 | 91 ± 2 |
| 3PPh | 3.3 ± 0.5 | 73 ± 5 | B[b]FA | 1.1 ± 0.1 | 91 ± 2 |
| 9PPh | 1.6 ± 0.2 | 61 ± 3 | B[j]FA | 1.8 ± 0.1 | 90 ± 2 |
| 2EN | UD | UD | |||
| 4Ebi | UD | UD | |||
| 4Pbi | UD | UD | |||
Fluorescence quenching was assayed using 1.0 μM P450 1B1 in 100 mM potassium phosphate buffer (pH 7.4) with 7 different concentrations of PAHs, and decreases in fluorescence intensities were measured at 331 nm (excitation at 295 nm). Ks values were estimated using hyperbolic or quadratic equations, as appropriate, with GraphPad Prism software (GraphPad Software, San Diego, CA). UD, undetectable due to interference with inhibitors. Bmax is the extrapolated % quenching. Results are presented as means ± S.E.