A 3D model of CYP1B1 explains the dominant 4-hydroxylation of estradiol.
CYP1A1 and CYP1A2 exhibit catalytic activity predominantly for the 2-hydroxylation of estradiol, whereas CYP1B1 exhibits catalytic activity predominantly for 4-hydroxylation of estradiol. To understand why CYP1B1 predominantly hydroxylates the 4-position of estradiol, we constructed three-dimensional structures of CYP1A1 and CYP1B1 by homology modeling, using the crystal structure of CYP1A2, and studied the docking mode of estradiol with CYP1A1, CYP1A2, and CYP1B1. The results demonstrated that two particular amino acid residues for each CYP, namely Thr124 and Phe260 of CYP1A2, Ser122 and Phe258 of CYP1A1, and Ala133 and Asn265 of CYP1B1, play an important role in estradiol recognition.
Itoh
Toshimasa
T
Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Takemura
Hitomi
H
Shimoi
Kayoko
K
Yamamoto
Keiko
K
D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry* / Q000378:metabolism*; D055162:Biocatalysis; D065633:Cytochrome P-450 CYP1B1; D004958:Estradiol / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D013379:Substrate Specificity
D004958:Estradiol; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1