title: The mechanism of a P-450 enzyme-aromatase; a molecular modelling perspective for the removal of the C(19) methyl and aromatisation of the steroid A ring.
abstract: The three possible mechanisms for the final step of aromatisation, as proposed by Wright and Akhtar, are studied using a molecular modelling approach utilising the 'substrate-heme complex' previously reported. The study considers the three mechanisms from a geometric point of view and concludes that only a ferroxy radical is involved in all three steps of aromatase action and not the mixture of both ferroxy and peroxy as previously suggested. The study also suggests that an alternative peroxy-based mechanism is unlikely due to the distances between reacting species. An alternative theoretical mechanism, which circumvents the production of the CHO. radical (regarded to be too small to be retained within the active site) for the final step of aromatisation is suggested involving the concerted breakup of the iron-formate complex together with hydrogen abstraction from C(1) of 3-hydroxy-estra-2,4-diene-17-one, resulting in oestrone and formic acid.
authors.affiliation: School of Applied Chemistry, Kingston University, Kingston upon Thames, Surrey, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000728:Androgens / Q000378:metabolism; D001141:Aromatase / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D004970:Estrone / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010545:Peroxides / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry; D012984:Software; D013256:Steroids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000728:Androgens; D005609:Free Radicals; D010545:Peroxides; D011166:Porphyrins; D013256:Steroids; D004970:Estrone; C049375:perhydroxyl radical; D007501:Iron; D001141:Aromatase