Compounds 4 and 5 were found to bind in the opposite direction of compounds 1 and 6. In those cases, the oxygen from the furan ring is located nearby the amino group of Asn297 (3.07 Å and 3.29 Å, respectively), while the oxygen from the coumarin moiety interact with the ferryl heme of the CYP2A6 (2.86 Å and 3.04 Å, and 3.07 Å and 3.74 Å, respectively). These results show that the active site region around Asn297 is quite narrow and cannot accommodate very large molecules. From all the studied psoralens with bulky groups at position 2, compound 1 is the only exception that was still able to bind similarly to the potent inhibitor xanthotoxin.