Role of P34S, G169R, R296C, and S486T Substitutions in Ligand Access and Catalysis for Cytochrome P450 2D6 Allelic Variants CYP2D6*14A and CYP2D6*14B.

In summary, the differential selectivity of CYP2D6*14 variants for the ligands (substrate and inhibitor) was governed by the alteration of the active site and access channel architecture induced by the natural mutations found in the alleles.