ERRγ tethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner
ERRγ tethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner
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DOI：
10.1016/j.bbrc.2008.06.050
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发表时间：
2008-08-29
影响因子：
3.1
通讯作者：
Shimohigashi, Yasuyuki
中科院分区：
文献类型：
--
作者：
Matsushima, Ayami;Teramoto, Takamasa;Shimohigashi, Yasuyuki
受体结合测定和 X 射线晶体结构分析表明，内分泌干扰物双酚 A (BPA) 与人雌激素相关受体 γ (ERR γ) 强烈结合。 BPA 很好地锚定在配体结合袋上，与其两个酚羟基形成氢键。在这项研究中，我们发现缺乏其中一个酚羟基的 4-α-枯基苯酚也与 ERR gamma 结合非常牢固。 4-α-枯基苯酚/ERRγ复合物的2.0埃晶体结构清楚地表明，ERRγ的Leu345-β-异丙基在4-α-枯基苯酚和BPA的紧密结合中发挥作用，以来回诱导配合方式旋转。 2008 Elsevier Inc. 保留所有权利。
A receptor-binding assay and X-ray crystal structure analysis demonstrated that the endocrine disruptor bisphenol A (BPA) strongly binds to human estrogen-related receptor gamma (ERR gamma). BPA is well anchored to the ligand-binding pocket, forming hydrogen bonds with its two phenol-hydroxyl groups. In this study, we found that 4-alpha-cumylphenol lacking one of its phenol-hydroxyl groups also binds to ERR gamma very strongly. The 2.0 angstrom crystal structure of the 4-alpha-cumylphenol/ERR gamma complex clearly revealed that ERR gamma's Leu345-beta-isopropyl plays a role in the tight binding of 4-alpha-cumylphenol and BPA, rotating in a back-and-forth induced-fit manner. 2008 Elsevier Inc. All rights reserved.