Interaction between Cytochrome P450 2B1 and Cytochrome b₅: Inhibition by synthetic peptides indicates a role for P450 residues Lys-122 and Arg-125

Binding of cytochrome b₅ to rat cytochrome P450 2B1 was inhibited (by 75%) by a synthetic peptide corresponding to P450 residues 116-134. The roles of Lys-122 and Arg-125 were evaluated using peptides in which one or both of these basic residues were replaced with Glu. The Lys-122 substitution nearly abolished while the Arg-125 replacement decreased (by 20%) the inhibitory potential of the peptide. Substitution of both residues resulted in a peptide with no inhibitory activity. These results thus indicate a role for a specific P450 region as well as two basic residues within this region In the cytochrome P450-cytochrome b₅ interaction.