A channel between the two domains leads to the active site where NADPH binds both domains and occupies a cleft that blocks access to the flavin group of FAD, which is bound to the large domain along the channel together with a water molecule. The nicotinamide group of NADPH interacts with the flavin group of FAD, and the NADPH binding site overlaps with the substrate binding site on the flavin group. FMOs contain several sequence motifs that are conserved across all domains: The FMO identifying motif interacts with the flavin of FAD. The F/LATGY motif is a sequence motif common in "N"-hydroxylating enzymes. The arginine residue interacts with the phosphate group of NADPH. The general function of these enzymes is to metabolise xenobiotics. Hence, they are considered to be xenobiotic detoxication catalysts. These proteins catalyze the oxygenation of multiple heteroatom-containing compounds that are present in our diet, such as amine-, sulfide-, phosphorus-, and other nucleophilic heteroatom-containing compounds. FMOs have been implicated in the metabolism of a number of pharmaceuticals, pesticides and toxicants, by converting the lipophilic xenobiotics into polar, oxygenated, and readily excreted metabolites. FMO substrates are structurally diverse compounds. However, they all share similar characteristics: Zwitterions, anions and dications are considered to be unfavorable substrates. There are several drugs reported to be typical substrates for FMOs. The majority of drugs function as alternate substrate competitive inhibitors to FMOs (i.e. good nucleophiles that compete with the drug for FMO oxygenation), since they are not likely to serve as FMO substrates. Only a few true FMO competitive inhibitors have been reported. Those include indole-3-carbinol and "N","N"-dimethylamino stilbene carboxylates. A well-known FMO inhibitor is methimazole (MMI). The FMO catalytic cycle proceeds as follows:  Expression of each type of FMO relies on several factors including, cofactor supply, physiological & environmental factors, as well as diet. Because of these factors, each type of FMO is expressed differently depending on the species and tissue. In humans, expression of FMO's is mainly concentrated to the human liver, lungs, and kidneys, where most of the metabolism of xenobiotics occur.