Review of the molecular modelling studies of the cytochrome P-450 estrogen synthetase enzyme, aromatase.
The biosynthesis of the family of female hormones, the estrogens, is mediated by the cytochrome P-450 based enzyme Aromatase (AR), an enzyme which has been the focus of extensive research for some time and has resulted in the synthesis of numerous inhibitory compounds with varying structural properties. The crystal structure of this membrane-bound enzyme has not been determined, although that of the bacterial P-450 camphor hydroxylase enzyme has, and the latter has been used for homology modelling of AR and other related enzymes. Several workers have attempted to obtain an approximate model of the active site of AR through the use of various molecular modelling techniques using inhibitors of this enzyme, as well as a combination of experiments involving active site mutagenesis of specific areas of the P-450 backbone together with molecular modelling. In this report these studies are reviewed. In summary, although the crystal structure of AR has yet to be determined, the use of molecular modelling studies has provided useful information in the design and synthesis of its inhibitors.
Ahmed
S
S
School of Applied Chemistry, Kingston University, Kingston upon Thames, Surrey, UK.
D001141:Aromatase / Q000737:chemistry*; D047072:Aromatase Inhibitors; D003461:Crystallography; D008958:Models, Molecular; D015394:Molecular Structure; D009153:Mutagens
D047072:Aromatase Inhibitors; D009153:Mutagens; D001141:Aromatase