Three-dimensional model of cytochrome P450 human aromatase |
| |
Authors: | Loge Cedric Le Borgne Marc Marchand Pascal Robert Jean-Michel Le Baut Guillaume Palzer Martina Hartmann Rolf W |
| |
Institution: | Department de Pharmacochimie, Biomolecules et Cibles Thérapeutiques, UPRES EA1155, UFR Sciences Pharmaceutiques, 1 rue Gaston Veil, F-44035 Nantes cedex 1, France. cedric.loge@univ-nantes.fr |
| |
Abstract: | A three-dimensional (3-D) structure of human aromatase (CYP 19) was modeled on the basis of the crystal structure of rabbit CYP2C5, the first solved X-ray structure of an eukaryotic cytochrome P450 and was evaluated by docking S-fadrozole and the steroidal competitive inhibitor (19R)-10-thiiranylestr-4-ene-3,17-dione, into the enzyme active site. According to a previous pharmacophoric hypothesis described in the literature, the cyano group of S-fadrozole partially mimics the steroid backbone C(17) carbonyl group of (19R)-10-thiiranylestr-4-ene-3,17-dione, and was oriented in a favorable position for H-bonding with the newly identified positively charged residues Lys 119 and Arg435. In addition, this model is consistent with the recent combined mutagenesis/modeling studies already published concerning the roles ofAsp309 and His480 in the aromatization of the steroid A ring. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|