Crystallization and preliminary X-ray diffraction studies of isoform alpha1 of the human thyroid hormone receptor ligand-binding domain.
Crystallization and preliminary X-ray diffraction studies of isoform alpha1 of the human thyroid hormone receptor ligand-binding domain.
复制标题
人甲状腺激素受体配体结合域亚型 α1 的结晶和初步 X 射线衍射研究。
DOI：
10.1107/s0907444904017858
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Polikarpov,I
中科院分区：
文献类型：
--
作者：
Nunes,FM;Aparicio,R;Santos,MAM;Portugal,RV;Dias,SMG;Neves,FAR;Simeoni,LA;Baxter,JD;Webb,P;Polikarpov,I
甲状腺激素受体（TR）在几乎所有组织中起着关键作用。TR配体结合结构域（LBD）通过激素结合诱导的构象变化参与重要的活动，如转录激活和抑制。获得了人甲状腺激素受体LBD（hTR α 1）亚型α 1与甲状腺激素T3和Triac复合物的两种晶型。hTR α 1-T3复合物以先前未观察到的晶体形式（空间群P212121，a = 59.98，B = 80.80，c = 102.21 °）结晶，在双阳极X射线源上衍射图案延伸至1.90 nm分辨率，空间群C2（a = 117.54，B = 80.66，c = 62.55 nm，β = 121.04 °），数据延伸至2.32 nm分辨率。 hTR α 1-三端双向可控硅复合物也在新的空间群P212121中结晶，晶胞参数a = 60.01，B = 80.82，c = 102.39 μ m;其分辨率极限扩展到2.20 μ m。 通过分子置换法进行了分相，目前正在进行结构改进。精细的结构可能为新的拟甲状腺药物的设计提供见解。
Thyroid hormone receptors (TR) play critical roles in virtually all tissues. The TR ligand-binding domain (LBD) participates in important activities, such as transcriptional activation and repression, through conformational changes induced by hormone binding. Two crystal forms of isoform α1 of the human thyroid hormone receptor LBD (hTRα1) in complex with the thyroid hormones T3 and Triac were obtained. The hTRα1–T3 complex was crystallized in a previously unobserved crystal form (space group P212121, a = 59.98, b = 80.80, c = 102.21 Å), with diffraction patterns extending to 1.90 Å resolution on a rotating-anode X-ray source, and in space group C2 (a = 117.54, b = 80.66, c = 62.55 Å, β = 121.04°), with data extending to 2.32 Å resolution. The hTRα1–Triac complex was also crystallized in the new space group P212121, with unit-cell parameters a = 60.01, b = 80.82, c = 102.39 Å; its resolution limit extended to 2.20 Å on a home source. Phasing was carried out by the molecular-replacement method and structural refinement is currently in progress. The refined structures may provide insight into the design of new thyromimetics.