A model for human cytochrome P450 2D6 based on homology modeling and NMR studies of substrate binding

The human cytochrome P450 2D6 (P450 2D6) was prepared by a baculovirus expression system, and then purified at 4 degrees C. A model of the complex of codeine with P450 2D6 was designed by combined homology modeling and distance restraints from paramagnetic relaxation calculations. Homology modeling involved the alignment of the P450 2D6 sequence against the multiple sequence and modification by Cameleon. In the model, the Asp 301 anionic residue forms an ion pair with the basic nitrogen of codeine.