Visualization of the parathyroid hormone receptor in long-active states
Visualization of the parathyroid hormone receptor in long-active states
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长时间活跃状态下甲状旁腺激素受体的可视化
DOI：
10.1016/j.medidd.2019.100001
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发表时间：
2019-06
影响因子：
--
通讯作者：
Jin-Peng Sun
中科院分区：
文献类型：
--
作者：
Zhao Yang;Jun-Yan Wang;Xiao Yu;Jin-Peng Sun
早在鱼类和鸟类等脊椎动物出现时就已出现的甲状旁腺激素受体（PTH1R），分别以内分泌或旁分泌方式响应甲状旁腺分泌的PTH和PTH相关肽（PTHrP）这两种内源性激素，在调节骨代谢和钙重吸收中发挥重要作用（图1）[1]。PTH1R在钙稳态调节中的关键作用使该受体成为治疗骨质疏松症的关键靶点，骨质疏松症是一种以骨微结构恶化为特征的疾病，影响全球超过1.5亿人，每年造成200万例骨折[2]。预计到2025年，欧盟骨质疏松症的成本将上升至468亿欧元[3]。目前可用的抗骨质疏松疗法包括特立哌齐和阿巴帕齐，它们分别是PTH和PTHrP的合成类似物[4，5]。然而，这些药物的肽性质限制了它们的使用，并且已经报道了很少有口服活性且更具成本效益的靶向PTH1R的有效小分子激动剂[6]。这一观察结果可能部分是由于缺乏以原子分辨率捕获配体结合状态的PTH1R的结构信息。
The parathyroid hormone receptor (PTH1R), which appeared as early as when vertebrates such as fish and birds emerged, plays important roles in the regulation of bone metabolism and calcium reabsorption in response to two endogenous hormones, PTH secreted from the parathyroid gland and PTH-related peptide (PTHrP), in an endocrine or paracrine manner respectively (Fig. 1)[1]. The critical role of PTH1R in the regulation of calcium homeostasis makes this receptor a key target in the treatment of osteoporosis, a disease characterized by deteriorative bone microarchitecture that affects more than 150 million people worldwide and is responsible for 2 million fractures annually [2]. The cost of osteoporosis in the European Union has been predicted to rise to€ 46.8 billion in 2025 [3]. Currently available antiosteoporosis therapies include teriparatide and abaloparatide, which are synthetic analogs of PTH and PTHrP, respectively [4, 5]. Nevertheless, the peptidic nature of these drugs limits their use, and few efficient small-molecule agonists targeting PTH1R that are orally active and more cost-effective have been reported [6]. This observation may be partially due to the lack of structural information that captures PTH1R in a ligand-bound state at atomic resolution.
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影响因子：
4.8
作者：
Luttrell LM;Maudsley S;Gesty-Palmer D
通讯作者：
Gesty-Palmer D
影响因子：
16.8
作者：
Ehrenmann, Janosch;Schoeppe, Jendrik;Plueckthun, Andreas
通讯作者：
Plueckthun, Andreas
影响因子：
56.9
作者：
Lihua Zhao;S. Ma;Ieva Sutkeviciute;D.-D. Shen-D.;X. E. Zhou;P. Waal;Chuankui Li;Yanyong Kang;Lisa J. Clark;F. Jean-Alphonse;A. White;Dongyong Yang;A. Dai;X. Cai;Jianmin Chen;Chun Xing Li;Y. Jiang;Tomoyuki Watanabe;T. Gardella;K. Melcher;Ming-Wei Wang;J. Vilardaga;H. E. Xu;Yan Zhang
通讯作者：
Lihua Zhao;S. Ma;Ieva Sutkeviciute;D.-D. Shen-D.;X. E. Zhou;P. Waal;Chuankui Li;Yanyong Kang;Lisa J. Clark;F. Jean-Alphonse;A. White;Dongyong Yang;A. Dai;X. Cai;Jianmin Chen;Chun Xing Li;Y. Jiang;Tomoyuki Watanabe;T. Gardella;K. Melcher;Ming-Wei Wang;J. Vilardaga;H. E. Xu;Yan Zhang
影响因子：
14.8
作者：
Ferrandon, Sebastien;Feinstein, Timothy N.;Castro, Marian;Wang, Bin;Bouley, Richard;Potts, John T.;Gardella, Thomas J.;Vilardaga, Jean-Pierre
通讯作者：
Vilardaga, Jean-Pierre
DOI：
10.1124/jpet.112.199752
发表时间：
2013-06-01
影响因子：
3.5
作者：
Cupp, Meghan E.;Nayak, Surendra K.;Thomsen, William J.
通讯作者：
Thomsen, William J.