The use of the novel substrate-heme complex approach in the derivation of a representation of the active site of the enzyme cholesterol side chain cleavage

The previously reported substrate-heme complex approach is used to study the binding of type II inhibitors of the enzyme cholesterol side chain cleavage (CSCC), a cytochrome P-450 dependent enzyme involved in the oxidative cleaveage of the C(20)-C(22) bond of cholesterol. Using the derived model, we have rationalised the inhibitory activity of a number of compounds including aminoglutethimide and pyridoglutethimide and the enantiomers of ketoconazole.