物理化学学报2012，Vol.28Issue(7)：1783-1789,7.DOI:10.3866/PKU.WHXB201204192
人甲状腺旁素1型受体的结构特征
Structural Characterization of Human Parathyroid Hormone 1 Receptor
林克江 1朱冬吉 1冷勇敢 1尤启冬1
作者信息
- 1. 中国药科大学药物化学教研室,南京210009
- 折叠
摘要
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 (TM)domain,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.关键词
甲状腺旁素1型受体/甲状腺旁素/同源模建/甲状腺旁素复合物Key words
Parathyroid hormone 1 receptor/Parathyroid hormone/Homology modeling/PTH-PTH 1R complex分类
化学化工引用本文复制引用
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(7):1783-1789,7.
