Influence of transmembrane helix mutations on cytochrome P450-membrane interactions and function (Biophysical Journal)

Human cytochrome P450 (CYP) enzymes play an important role in the metabolism of drugs, steroids, fatty acids and xenobiotics. Microsomal CYPs are anchored in the ER membrane by an N-terminal transmembrane (TM) helix that is connected to the globular catalytic domain by a flexible linker sequence. However, the structural and functional importance of the TM-helix is unclear since it has been shown that CYPs can still associate with the membrane and have enzymatic activity in reconstituted systems after truncation or modification of the N-terminal sequence.