Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid receptor 2
文献类型：期刊论文
| Author | Zhu, Shengnan3,7,8; Yuan, Qingning6,7; Li, Xinzhu5; He, Xinheng7; Shen, Shiyi7; Wang, Dongxue4; Li, Junrui7; Cheng, Xi1,7; Duan, Xiaoqun3,8; Xu, H. Eric2,5,7
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| Source | CELL REPORTS
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| Issued Date | 2023-11-28 |
| Volume | 42Issue:11Pages:19 |
| Keyword | different ligands recognition ligand selectivity receptor |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2023.113406 |
| Corresponding Author | Duan, Xiaoqun(robortduan@163.com) ; Xu, H. Eric(eric.xu@simm.ac.cn) ; Duan, Jia(duanjia@simm.ac.cn) |
| English Abstract | Niacin, an age-old lipid-lowering drug, acts through the hydroxycarboxylic acid receptor 2 (HCAR2), a G-protein-coupled receptor (GPCR). Yet, its use is hindered by side effects like skin flushing. To address this, specific HCAR2 agonists, like MK-6892 and GSK256073, with fewer adverse effects have been created. However, the activation mechanism of HCAR2 by niacin and these new agonists is not well understood. Here, we present three cryoelectron microscopy structures of Gi-coupled HCAR2 bound to niacin, MK-6892, and GSK256073. Our findings show that different ligands induce varying binding pockets in HCAR2, influenced by aromatic amino acid clusters (W91ECL1, H1614.59, W1885.38, H1895.39, and F1935.43)from receptors ECL1, TM4, and TM5. Additionally, conserved residues R1113.36 and Y2847.43, unique to the HCA receptor family, likely initiate activation signal propagation in HCAR2. This study provides insights into ligand recognition, re-ceptor activation, and G protein coupling mediated by HCAR2, laying the groundwork for developing HCAR2-targeted drugs. |
| WOS Keyword | NICOTINIC-ACID ; BAYESIAN-APPROACH ; GPR109A ; DISCOVERY ; IDENTIFICATION ; AGONISTS ; POTENT |
| Funding Project | Shanghai Institute of Materia Medica (SIMM) ; Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Sci- ence and Technology Major Project ; CAS Strategic Priority Research Program[XDB37030103] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82373881] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; Shanghai Sailing Program[23YF1456800] ; Guangxi Science and Technology Major Project[2021AA16003] |
| WOS Research Area | Cell Biology |
| Language | 英语 |
| WOS ID | WOS:001112089200001 |
| Publisher | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308101]  |
| Collection | 新药研究国家重点实验室 |
| Corresponding Author | Duan, Xiaoqun; Xu, H. Eric; Duan, Jia |
| Affiliation | 1.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Guilin Med Univ, Dept Pharmacol, Guilin 541004, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.Macau Univ Sci & Technol, Fac Med, Sch Pharm, Macau 999078, Peoples R China |
| Recommended Citation GB/T 7714 | Zhu, Shengnan,Yuan, Qingning,Li, Xinzhu,et al. Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid receptor 2[J]. CELL REPORTS,2023,42(11):19. |
| APA | Zhu, Shengnan.,Yuan, Qingning.,Li, Xinzhu.,He, Xinheng.,Shen, Shiyi.,...&Duan, Jia.(2023).Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid receptor 2.CELL REPORTS,42(11),19. |
| MLA | Zhu, Shengnan,et al."Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid receptor 2".CELL REPORTS 42.11(2023):19. |
入库方式： OAI收割
来源：上海药物研究所
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