1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

The interaction of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with cytochrome P450 2D6 (CYP 2D6) was analyzed via nuclear magnetic resonance spectroscopy to characterize the mode of binding of the neurotoxin. The mode of binding of MPTP with CYP 2D6 and the resulting products of the interaction were altered by the addition of human nicotinamide reduced adenine dinucleotide phosphate-cytochrome P450 reductase. Furthermore, the interaction between the two enzymes induced an allosteric change in the active site of CYP 2D6.