Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Recognition of methamphetamine and other amines by trace amine receptor TAAR1.
Journal, issue, pages	Nature, Vol. 624, Issue 7992, Page 663-671, Year 2023
Publish date	Nov 7, 2023
Authors	Heng Liu / You Zheng / Yue Wang / Yumeng Wang / Xinheng He / Peiyu Xu / Sijie Huang / Qingning Yuan / Xinyue Zhang / Ling Wang / Kexin Jiang / Hong Chen / Zhen Li / Wenbin Liu / Sheng Wang / H Eric Xu / Fei Xu /
PubMed Abstract	Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the ...Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the endogenous β-phenylethylamine (β-PEA) as well as methamphetamine, an abused substance that has posed a severe threat to human health and society. Given its unique physiological role in the brain, TAAR1 is also an emerging target for a range of neurological disorders including schizophrenia, depression and drug addiction. Here we report structures of human TAAR1-G-protein complexes bound to methamphetamine and β-PEA as well as complexes bound to RO5256390, a TAAR1-selective agonist, and SEP-363856, a clinical-stage dual agonist for TAAR1 and serotonin receptor 5-HTR (refs. ). Together with systematic mutagenesis and functional studies, the structures reveal the molecular basis of methamphetamine recognition and underlying mechanisms of ligand selectivity and polypharmacology between TAAR1 and other monoamine receptors. We identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in the ligand-binding pockets, which may contribute to the ligand recognition in TAAR1. These findings shed light on the ligand recognition mode and activation mechanism for TAAR1 and should guide the development of next-generation therapeutics for drug addiction and various neurological disorders.
External links	Nature / PubMed:37935377
Methods	EM (single particle)
Resolution	2.6 - 3.0 Å
Structure data	37347 8w87 EMDB-37347, PDB-8w87: Cryo-EM structure of the METH-TAAR1 complex Method: EM (single particle) / Resolution: 2.8 Å 37348 8w88 EMDB-37348, PDB-8w88: Cryo-EM structure of the SEP363856-bound TAAR1-Gs complex Method: EM (single particle) / Resolution: 2.6 Å 37349 8w89 EMDB-37349, PDB-8w89: Cryo-EM structure of the PEA-bound TAAR1-Gs complex Method: EM (single particle) / Resolution: 3.0 Å 37350 8w8a EMDB-37350, PDB-8w8a: Cryo-EM structure of the RO5256390-TAAR1 complex Method: EM (single particle) / Resolution: 2.8 Å 37351 8w8b EMDB-37351, PDB-8w8b: Cryo-EM structure of SEP-363856 bounded serotonin 1A (5-HT1A) receptor-Gi protein complex Method: EM (single particle) / Resolution: 3.0 Å
Chemicals	ChemComp-B40: (2S)-N-methyl-1-phenylpropan-2-amine / Methamphetamine ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-UJL: 1-[(7~{S})-5,7-dihydro-4~{H}-thieno[2,3-c]pyran-7-yl]-~{N}-methyl-methanamine ChemComp-PEA: 2-PHENYLETHYLAMINE / alkaloidYM / Phenethylamine ChemComp-HOH: WATER / Water ChemComp-T5U: (4S)-4-[(2S)-2-phenylbutyl]-1,3-oxazolidin-2-imine ChemComp-PLM*: PALMITIC ACID / Palmitic acid
Source	homo sapiens (human) lama glama (llama) escherichia coli (E. coli)
Keywords	MEMBRANE PROTEIN / TAAR1 / METH / GPCR / SEP-363856 / antipsychotics / PEA / R05256390 / 5-HT1A / SEP363856