中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs

文献类型：期刊论文

作者Wang, James Jiqi4,5,6; Jin, Sanshan2,3; Zhang, Heng6; Xu, Youwei6; Hu, Wen6; Jiang, Yi2,3; Chen, Chen4,5; Wang, Dao Wen4,5; Xu, H. Eric1,2,6; Wu, Canrong6
刊名SCIENCE ADVANCES
出版日期2024-02-09
卷号10期号:6页码:11
ISSN号2375-2548
DOI10.1126/sciadv.adk5184
通讯作者Wang, Dao Wen(wucanrong@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn) ; Wu, Canrong(dwwang@tjh.tjmu.edu.cn)
英文摘要The prostacyclin (PGI(2)) receptor (IP) is a G(s)-coupled receptor associated with blood pressure regulation, allergy, and inflammatory response. It is a main therapeutic target for pulmonary arterial hypertension (PAH) and several other diseases. Here we report cryo-electron microscopy (cryo-EM) structures of the human IP-G(s) complex bound with two anti-PAH drugs, treprostinil and MRE-269 (active form of selexipag), at global resolutions of 2.56 and 2.41 angstrom, respectively. These structures revealed distinct features governing IP ligand binding, receptor activation, and G protein coupling. Moreover, comparison of the activated IP structures uncovered the mechanism and key residues that determine the superior selectivity of MRE-269 over treprostinil. Combined with molecular docking and functional studies, our structures provide insight into agonist selectivity, ligand recognition, receptor activation, and G protein coupling. Our results provide a structural template for further improving IP-targeting drugs to reduce off-target activation of prostanoid receptors and adverse effects.
WOS关键词CRYO-EM STRUCTURE ; PROSTANOID RECEPTORS ; MANAGEMENT ; SOFTWARE ; SURVIVAL ; THERAPY ; BINDING
资助项目CAS Strategic Priority Research Program[XDB37030103] ; National Natural Science Foundation of China[32301016] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[32171187] ; National Natural Science Foundation of China[82330010] ; National Natural Science Foundation of China[81902085] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; National Key R&D Program of China[2022YFC2703105] ; China Postdoctoral Science Foundation Funded Project[2021M703342] ; Shanghai Post-doctoral Excellence Program[2021429] ; Key tasks of Lingang Laboratory[LG202101-01-03] ; Key tasks of Lingang Laboratory[LG202101-01-640] ; Key tasks of Lingang Laboratory[LG-GG-202204-01] ; Sanofi Scholarship Program
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001189871700005
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/310532]  
专题新药研究国家重点实验室
通讯作者Wang, Dao Wen; Xu, H. Eric; Wu, Canrong
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Lingang Lab, Shanghai 200031, Peoples R China
4.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hubei Key Lab Genet & Mol Mech Cardiol Disorders, Wuhan 430000, Peoples R China
5.Huazhong Univ Sci & Technol, Dept Internal Med, Div Cardiol, Wuhan 430000, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wang, James Jiqi,Jin, Sanshan,Zhang, Heng,et al. Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs[J]. SCIENCE ADVANCES,2024,10(6):11.
APA Wang, James Jiqi.,Jin, Sanshan.,Zhang, Heng.,Xu, Youwei.,Hu, Wen.,...&Wu, Canrong.(2024).Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs.SCIENCE ADVANCES,10(6),11.
MLA Wang, James Jiqi,et al."Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs".SCIENCE ADVANCES 10.6(2024):11.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。