EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.
ジャーナル・号・ページ	Cell, Vol. 186, Issue 24, Page 5347-5362.e24, Year 2023
掲載日	2023年11月22日
著者	Pan Shang / Naikang Rong / Jing-Jing Jiang / Jie Cheng / Ming-Hui Zhang / Dongwei Kang / Lei Qi / Lulu Guo / Gong-Ming Yang / Qun Liu / Zhenzhen Zhou / Xiao-Bing Li / Kong-Kai Zhu / Qing-Biao Meng / Xiang Han / Wenqi Yan / Yalei Kong / Lejin Yang / Xiaohui Wang / Dapeng Lei / Xin Feng / Xinyong Liu / Xiao Yu / Yue Wang / Qian Li / Zhen-Hua Shao / Fan Yang / Jin-Peng Sun /
PubMed 要旨	Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment ...Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.
リンク	Cell / PubMed:37963465
手法	EM (単粒子)
解像度	2.9 - 3.48 Å
構造データ	37429 8wc3 EMDB-37429, PDB-8wc3: Cryo-EM structure of the SEP363856-bound mTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 3.0 Å 37430 8wc4 EMDB-37430, PDB-8wc4: Cryo-EM structure of the ZH8651-bound mTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 3.1 Å 37431 8wc5 EMDB-37431, PDB-8wc5: Cryo-EM structure of the TMA-bound mTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 3.3 Å 37432 8wc6 EMDB-37432, PDB-8wc6: Cryo-EM structure of the PEA-bound mTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 3.2 Å 37433 8wc7 EMDB-37433, PDB-8wc7: Cryo-EM structure of the ZH8667-bound mTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 3.1 Å 37434 8wc8 EMDB-37434, PDB-8wc8: Cryo-EM structure of the ZH8651-bound hTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 2.9 Å 37435 8wc9 EMDB-37435, PDB-8wc9: Cryo-EM structure of the ZH8651-bound mTAAR1-Gq complex 手法: EM (単粒子) / 解像度: 3.2 Å 37436 8wca EMDB-37436, PDB-8wca: Cryo-EM structure of the PEA-bound hTAAR1-Gs complex 手法: EM (単粒子) / 解像度: 3.48 Å 37437 8wcb EMDB-37437, PDB-8wcb: Cryo-EM structure of the CHA-bound mTAAR1-Gq complex 手法: EM (単粒子) / 解像度: 3.1 Å 37438 8wcc EMDB-37438, PDB-8wcc: Cryo-EM structure of the CHA-bound mTAAR1 complex 手法: EM (単粒子) / 解像度: 3.04 Å
化合物	ChemComp-UJL: 1-[(7~{S})-5,7-dihydro-4~{H}-thieno[2,3-c]pyran-7-yl]-~{N}-methyl-methanamine ChemComp-VMT: 2-(4-bromophenyl)ethanamine / 4-ブロモフェネチルアミン ChemComp-TMA: TETRAMETHYLAMMONIUM ION / テトラメチルアンモニウム ChemComp-PEA: 2-PHENYLETHYLAMINE / フェネチルアンモニウム / alkaloidYM ChemComp-VMK: 2-[4-(3-fluorophenyl)phenyl]ethanamine ChemComp-HAI*: CYCLOHEXYLAMMONIUM ION / シクロヘキシルアミニウム
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ) synthetic construct (人工物)
キーワード	MEMBRANE PROTEIN / SEP363856 / mTAAR1 / ZH8651 / Gq / TMA / PEA / ZH8667 / hTAAR1 / Gs / CHA