The role of cytochrome P450 2B6 and 2B4 substrate access channel residues predicted based on crystal structures of the amlodipine complexes.

•Absorbance spectroscopy revealed two amlodipine binding events in solution with P450 2B6 and 2B4.•The results are in agreement with recently solved X-ray structures of the amlodipine complexes.•The function of access channel residues was determined by site-directed mutagenesis and steady-state kinetics.•R73 in P450 2B6 and R73, V216, L219, and F220 in 2B4 are important for catalytic efficiency.