A 3D Model of CYP1B1 Explains the Dominant 4-Hydroxylation of Estradiol
A 3D Model of CYP1B1 Explains the Dominant 4-Hydroxylation of Estradiol
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DOI：
10.1021/ci1000554
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发表时间：
2010-06-01
影响因子：
5.6
通讯作者：
Yamamoto, Keiko
中科院分区：
文献类型：
--
作者：
Itoh, Toshimasa;Takemura, Hitomi;Yamamoto, Keiko
CYP1A1和CYP1A2主要催化雌二醇的2-羟基化反应，而CYP1B1主要催化雌二醇的4-羟基化反应。为了了解为什么CYP1B1主要羟化雌二醇的4位，我们利用CYP1A2的晶体结构，通过同源建模构建了CYP1A1和CYP1B1的三维结构，并研究了雌二醇与CYP1A1、CYP1A2和CYP1B1的对接模式。结果表明，细胞色素P1A2的Thr124和Phe260，细胞色素P1A1的Ser122和Phe258，细胞色素P1B1的Ala133和Asn265这两个氨基酸残基在雌二醇识别中起重要作用。
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.