Figure 1.
The position demethylated by CYP is indicated by a dashed line.
Table 1.
Mutation and activity of the wild-type and mutants of CYP2B6 used in this study.
Figure 2.
RMSDs for two mutants of CYP2B6.
RMSD of CYP2B6.4 (A) converged, whereas that of CYP2B6.12 (B) did not converge at 20 ns.
Figure 3.
RMSF of the Cα atoms in the wild-type.
The highest peak was Thr255. Around the highest peak, there are RMSF peaks at those for Tyr226 and Ala279. An additional peak is observed at the peak for Asn417.
Figure 4.
RMSFs of the Cα atoms in mutants.
(A) CYP2B6.4, (B) CYP2B6.8, (C) CYP2B6.11, (D) CYP2B6.12, (E) CYP2B6. 15, (F) CYP2B6. 18, (G) CYP2B6.21, and (H) CYP2B6.24. In some mutants, the locations and heights of the peaks are different from those in the wild-type. A prominent peak is observed at 100–200th residues in some mutants but not in the wild-type.
Figure 5.
The structure of CYP2B6 shown by a ribbon diagram.
The helices near the substrate recognition site, C, I, and L helices, are shown in purple.
Figure 6.
Ribbon-and-stick diagram showing the C/D loop (yellow) and the G/H loop (purple).
(A) CYP2B6.8. (B) CYP2B6.11. The relative position of the C/D and the G/H loop differs dramatically among mutants.
Figure 7.
Ribbon-and-stick diagram showing the I helix and the heme of the CYP2B6 wild-type (blue) and CYP2B6.12 variant (purple).
Figure 8.
CYP2B6.1 and CYP2B6.8 colored for isotropic displacement.
The larger value of the isotropic displacement is indicated by red.
Figure 9.
Structure of the complex between the wild-type and AM after docking simulation.
(A) The whole complex structure. CYP2B6.1 is shown by ribbon, heme and AM are shown by ball-and-stick representation. AM is circled. (B) Structure around the active site. The residues of CYP2B6.1 are shown by stick, heme and AM are shown by ball-and-stick representation.
Figure 10.
Structure of the helices around the heme.
The C, D, E, G, H, and I helices of the CYP2B6 wild-type (blue) and CYP2B6.18 variant (purple) are shown by ribbons; the heme is shown by ball-and-stick representation.
Figure 11.
Ligand binding pocket of CYP2B6.18 detected by HBOP and HBSITE.
The binding pocket is illustrated by probe spheres.
Figure 12.
Hydrogen bond between AM and Thr302 in CYP2B6.8.
Figure 13.
Ligand binding pockets of CYP2B6.1 (light blue) and CYP2B6.4 (brown).
The pockets is illustrated by probe spheres.