Three-dimensional models of estrogen receptor ligand binding domain complexes, based on related crystal structures and mutational and structure-activity relationship data.
Three-dimensional models of estrogen receptor ligand binding domain complexes, based on related crystal structures and mutational and structure-activity relationship data.
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雌激素受体配体结合域复合物的三维模型，基于相关晶体结构以及突变和结构-活性关系数据。
DOI：
10.1021/jm970406v
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发表时间：
1998
影响因子：
7.3
通讯作者：
A. Mueller
中科院分区：
文献类型：
--
作者：
J. Wurtz;U. Egner;N. Heinrich;D. Moras;A. Mueller
基于最近确定的视黄酸核受体（NRs）的配体结合域（LBD）的晶体结构，我们提出了人类雌激素受体α (herα) LBD的三维（3D）分子模型。对影响结合特性的突变体进行了文献检索；在已发表的48个突变体中，有45个可以在模型的基础上得到满意的解释。雌二醇被安置在结合袋中，以探测其与蛋白质的相互作用。对不同的配体取向进行了能量最小化和分子动力学计算。为了评估它们的质量，使用已知的结构-活性关系（SAR）数据对选择的雌二醇同源物进行了不同的模型评分。这两个最好的模型在很大程度上解释了亲缘关系较远的配体的结合亲和力。
On the basis of the recently determined crystal structures of the ligand binding domains (LBDs) of the retinoic acid nuclear receptors (NRs), we present a three-dimensional (3D) molecular model of the human estrogen receptor alpha (hERalpha) LBD. A literature search for mutants affecting the binding properties has been performed; 45 out of 48 published mutants can be explained satisfactorily on the basis of the model. Estradiol has been docked into the binding pocket to probe its interactions with the protein. Energy minimizations and molecular dynamics calculations were performed for various ligand orientations. To evaluate their quality, the different models were scored using known structure-activity relationship (SAR) data for selected close estradiol homologues. The two best models explain largely the binding affinities of more distantly related ligands.