期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 106, 期 -, 页码 901-907出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2017.08.088
关键词
GPR17; Ligand-docking; CAMP; MDL29951; AC1MLNKK; T0510.3657
资金
- Academy of Finland
G Protein-coupled Receptor 17 (GPR17) is phylogenetically related to the purinergic receptors emerged as a potential drug target for multiple sclerosis, Parkinson disease, Alzheimer disease and cancer. Unfortunately, the crystal structure of GPR17 is unresolved. With the interest in structure-based ligand discovery, we modeled the structure of GPR17. The model allowed us to identify two novel agonists, AC1MLNKK and T0510.3657 that selectively activate GPR17 which exhibit better interaction properties than previously known ligand, MDL29951. We report detailed protein-ligand interactions and the dynamics of GPR17-ligand interaction by molecular docking and molecular dynamics experiments. Ex vivo validation of GPR17-ligand interaction provides evidence that ligand T0510-3657 and AC1MLNKK inhibit the cAMP levels in GPR17-HEK293T cells, with a pEC(50) of 4.79 and 4.64, respectively. In silico and ex vivo validation experiments provided the deep understanding of ligand binding with GPR17 and the present findings reported here may lead to use these two compounds as a potential activator of GPR17 for therapeutic intervention. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据