Structural evidence for ligand specificity in the binding domain of the human androgen receptor -: Implications for pathogenic gene mutations
Structural evidence for ligand specificity in the binding domain of the human androgen receptor -: Implications for pathogenic gene mutations
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DOI：
10.1074/jbc.m004571200
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发表时间：
2000-08-25
影响因子：
4.8
通讯作者：
Carrondo, MA
中科院分区：
文献类型：
--
作者：
Matias, PM;Donner, P;Carrondo, MA
人雄激素受体（hAR）和人孕激素受体配体结合结构域与相同的配体美曲勃龙（R1881）的复合物的晶体结构已被确定。这两种三维结构都显示出典型的核受体折叠。人孕酮受体与hAR之间的配体结合口袋中两个残基的变化最可能是R1881对hAR的特异性的来源。分析了与前列腺癌或部分或完全雄激素受体不敏感综合征相关的hAR配体结合域的配体结合口袋中14个已知突变的结构意义。这些突变体中的大多数的影响可以解释的晶体结构的基础上。
The crystal structures of the human androgen receptor (hAR) and human progesterone receptor ligand-binding domains in complex with the same ligand metribolone (R1881) have been determined. Both three-dimensional structures show the typical nuclear receptor fold. The change of two residues in the ligand-binding pocket between the human progesterone receptor and hAR is most likely the source for the specificity of R1881 to the hAR. The structural implications of the 14 known mutations in the ligand-binding pocket of the hAR ligand-binding domains associated with either prostate cancer or the partial or complete androgen receptor insensitivity syndrome were analyzed. The effects of most of these mutants could be explained on the basis of the crystal structure.