A DETAILED MOLECULAR-MODEL FOR HUMAN AROMATASE

Using a variety of techniques, including sequence alignment, secondary structure prediction, molecular mechanics and molecular dynamics, we have constructed a model for the three-dimensional structure of P-450a rom (human aromatase) based on that of P-450cam, the only cytochrome P -450 enzyme for which the crystal structure is known. The predicted st ructure is found to be in good agreement with current experimental dat a; both direct, from site-directed mutagenesis studies, and indirect, from the consideration of the structures and activities of known subst rates and inhibitors.