人甲状腺旁素1型受体的结构特征

引用本文: 林克江, 朱冬吉, 冷勇敢, 尤启冬. 人甲状腺旁素1型受体的结构特征[J]. 物理化学学报, 2012, 28(07): 1783-1789. doi: 10.3866/PKU.WHXB201204192 shu

Citation: LIN Ke-Jiang, ZHU Dong-Ji, LENG Yong-Gan, YOU Qi-Dong. Structural Characterization of Human Parathyroid Hormone 1 Receptor[J]. Acta Physico-Chimica Sinica, 2012, 28(07): 1783-1789. doi: 10.3866/PKU.WHXB201204192 shu

人甲状腺旁素1型受体的结构特征

摘要:

人甲状腺旁素1 型受体(PTH1R)是骨形成相关的B类G蛋白偶联受体, 其底物甲状腺旁腺素(PTH)及类似物具有抗骨质疏松作用. 由于此类受体的三维结构难以进行实验测定, 本文采用同源模建的方法, 完整构建了胞外区、跨膜区及其它相关区域, 并通过对接研究, 阐明复合物的氢键、疏水性相互作用及其与底物的相互作用关系和关键位点. 为进一步设计和发展此类药物提供理论依据.

关键词:

English

Structural Characterization of Human Parathyroid Hormone 1 Receptor

1.
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, P. R. China
Received Date: 22 February 2012
Available Online: 07 June 2012

Abstract:

Parathyroid hormone 1 receptor (PTH1R) is a member of the class B G-protein coupled receptor (B-GPCR) family and is involved in bone formation. Its substrate parathyroid hormone (PTH) and its analogues are being developed as anti-osteoporosis therapeutics. The structure-based rational drug design of PTH1R substrates has been hampered by the lack of experimentally determined three-dimensional (3D) structures from techniques such as nuclear magnetic resonance (NMR) and X-ray crystallography. Here, we have constructed a 3D model of PTH1R including its extracellular domain (ECD), transmembrane domain (TM) and other domains using a homology modeling approach. In addition, to capture the ligand-receptor interactions, we have manually docked human parathyroid hormone (1-34) into the top scoring receptor model, and subjected the PTH-PTH1R complex to an unconstrained energy minimization. The integral 3D receptor model provides an easier way to understand the interactions involved at the TM, ECD, and other domains. Furthermore, the parameters of hydrogen bonding, hydrophobic, and other interactions from the ligand-receptor model, enabled us to elucidate the important interactions between PTH (1-34) and PTH1R. This ligand-receptor model could potentially serve as a tool for structure-based virtual screening in the development of non-peptide based anti-osteoporosis drugs.

Key words:

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沈阳化工大学材料科学与工程学院沈阳 110142

人甲状腺旁素1型受体的结构特征

English

Structural Characterization of Human Parathyroid Hormone 1 Receptor

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

人甲状腺旁素1型受体的结构特征

English

Structural Characterization of Human Parathyroid Hormone 1 Receptor

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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