Structural basis for ligand recognition of the human thromboxane A(2) receptor
文献类型：期刊论文
| 作者 | Fan, Hengxin1,2,3,7; Chen, Shuanghong1,2,7; Yuan, Xiaojing2,7; Han, Shuo1,7; Zhang, Hui1,2,7; Xia, Weiliang4; Xu, Yechun2,7 ; Zhao, Qiang1,2,5,6,7; Wu, Beili2,3,5,6,7
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| 刊名 | NATURE CHEMICAL BIOLOGY
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| 出版日期 | 2019-01 |
| 卷号 | 15期号:1页码:27-+ |
| ISSN号 | 1552-4450 |
| DOI | 10.1038/s41589-018-0170-9 |
| 文献子类 | Article |
| 英文摘要 | Stimulated by thromboxane A(2), an endogenous arachidonic acid metabolite, the thromboxane A(2) receptor (TP) plays a pivotal role in cardiovascular homeostasis, and thus is considered as an important drug target for cardiovascular disease. Here, we report crystal structures of the human TP bound to two nonprostanoid antagonists, ramatroban and daltroban, at 2.5 angstrom and 3.0 angstrom resolution, respectively. The TP structures reveal a ligand-binding pocket capped by two layers of extracellular loops that are stabilized by two disulfide bonds, limiting ligand access from the extracellular milieu. These structures provide details of interactions between the receptor and antagonists, which help to integrate previous mutagenesis and SAR data. Molecular docking of prostanoid-like ligands, combined with mutagenesis, ligand-binding and functional assays, suggests a prostanoid binding mode that may also be adopted by other prostanoid receptors. These insights into TP deepen our understanding about ligand recognition and selectivity mechanisms of this physiologically important receptor. |
| WOS关键词 | SITE-DIRECTED MUTAGENESIS ; 2ND EXTRACELLULAR LOOP ; CRYSTAL-STRUCTURE ; PROSTANOID RECEPTORS ; SIGNAL-TRANSDUCTION ; ANTAGONIST ; PROTEIN ; BINDING ; ACID ; IDENTIFICATION |
| 资助项目 | National Key R&D Program of China[2018YFA0507000] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-SMC024] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-SMC054] ; National Science Foundation of China[31825010] ; National Science Foundation of China[81525024] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000452634100012 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279461]  |
| 专题 | 新药研究国家重点实验室 药物靶标结构与功能中心 |
| 通讯作者 | Zhao, Qiang; Wu, Beili |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 2.Univ Chinese Acad Sci, Beijing, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai, Peoples R China; 5.Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai, Peoples R China; 6.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Beijing, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Fan, Hengxin,Chen, Shuanghong,Yuan, Xiaojing,et al. Structural basis for ligand recognition of the human thromboxane A(2) receptor[J]. NATURE CHEMICAL BIOLOGY,2019,15(1):27-+. |
| APA | Fan, Hengxin.,Chen, Shuanghong.,Yuan, Xiaojing.,Han, Shuo.,Zhang, Hui.,...&Wu, Beili.(2019).Structural basis for ligand recognition of the human thromboxane A(2) receptor.NATURE CHEMICAL BIOLOGY,15(1),27-+. |
| MLA | Fan, Hengxin,et al."Structural basis for ligand recognition of the human thromboxane A(2) receptor".NATURE CHEMICAL BIOLOGY 15.1(2019):27-+. |
入库方式： OAI收割
来源：上海药物研究所
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