人3型3α-羟基类固醇脱氢酶的结晶及1.8埃分辨率下的初步X射线晶体学分析。

Crystallization and preliminary X-ray crystallographic analysis of the human type 3 3 alpha-hydroxysteroid dehydrogenase at 1.8 A resolution.

作者信息

Zhu D W, Cantin L, Nahoum V, Rehse P, Luu-The V, Labrie F, Breton R, Lin S X

机构信息

Medical Research Council Group in Molecular Endocrinology, CHUL Research Center and Laval University, 2705 Boulevard Laurier, Québec G1V 4G2, Canada.

出版信息

Acta Crystallogr D Biol Crystallogr. 2001 Apr;57(Pt 4):589-91. doi: 10.1107/s0907444901001160.

DOI:10.1107/s0907444901001160

PMID:11264591

Abstract

In androgen-sensitive target tissues, 3 alpha-hydroxysteroid dehydrogenase regulates the androgen receptor (AR) activity by catalyzing the inactivation of 5 alpha-dihydrotestosterone (the most natural potent androgen) to 5 alpha-androstane-3 alpha,17 beta-diol. In this report, the crystallization of a human prostatic type 3 3 alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamily, is described. Two different crystal forms of the complex between the human type 3 3 alpha-HSD, NADP(+) and testosterone have been obtained using PEG as precipitant. Crystal form I, which diffracts to 1.6 A, belongs to the monoclinic space group P2(1), with unit-cell parameters a = 55.07, b = 87.15, c = 76.88 A, beta = 107.37 degrees and two subunits in the asymmetric unit. A complete data set has been collected at 1.8 A. Crystal form II, which diffracts to 2.6 A, belongs to the rhombohedral space group R32, with unit-cell parameters a = b = 143.59, c = 205.86 A, alpha = beta = 90, gamma = 120 degrees and two subunits in the asymmetric unit.

摘要

在雄激素敏感的靶组织中，3α-羟基类固醇脱氢酶通过催化将5α-二氢睾酮（最具天然活性的雄激素）失活为5α-雄甾烷-3α,17β-二醇来调节雄激素受体（AR）的活性。在本报告中，描述了人前列腺型3 3α-羟基类固醇脱氢酶（醛酮还原酶超家族的一员）的结晶情况。使用聚乙二醇作为沉淀剂，已获得人3型3α-HSD、NADP(+)和睾酮之间复合物的两种不同晶体形式。晶体形式I的衍射分辨率为1.6 Å，属于单斜空间群P2(1)，晶胞参数a = 55.07，b = 87.15，c = 76.88 Å，β = 107.37°，不对称单元中有两个亚基。已在1.8 Å下收集了完整的数据集。晶体形式II的衍射分辨率为2.6 Å，属于菱面体空间群R32，晶胞参数a = b = 143.59，c = 205.86 Å，α = β = 90°，γ = 120°，不对称单元中有两个亚基。