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	Structure-based design of subtype-selective psychedelic analogs.
Journal, issue, pages	Nat Commun, Vol. 17, Issue 1, Year 2026
Publish date	Sep 17, 2026
Authors	Huiqiong Li / Lingjie Tang / Jinfeng Zhang / Bing Meng / Dongmei Cao / Yujin Chen / Jing Yu / Huan Wang / Zhi-Jie Liu / Sheng Wang / Jianjun Cheng /
PubMed Abstract	Classical psychedelics exert hallucinogenic and therapeutic effects primarily through activation of serotonin 2 A receptor (5-HTR), offering promise as transformative treatments for ...Classical psychedelics exert hallucinogenic and therapeutic effects primarily through activation of serotonin 2 A receptor (5-HTR), offering promise as transformative treatments for neuropsychiatric disorders. However, their concurrent activation of 5-HTR-associated with cardiac valvulopathy-raises serious safety concerns, underscoring the need for subtype-selective psychedelics. To address this, we determine the cryo-EM structure of 5-HTR and perform a comparative structural analysis of the orthosteric binding pockets (OBPs) of 5-HTR and 5-HTR. Guided by key residue differences, we develop a trigonal pharmacophore model to inform the design of 5-HTR-selective agonists that avoid 5-HTR activation. Using this model, we design and synthesize two compound series that selectively activate 5-HTR while antagonizing 5-HTR. Molecular basis of subtype selectivity is confirmed by five additional cryo-EM structures of receptor-ligand complexes. Selected compounds also exhibit antidepressant-like efficacy in animal models. Our findings provide a strategy for the development of safer, subtype-selective psychedelic analogs with therapeutic potential.
External links	Nat Commun / PubMed:42754591 / PubMed Central
Methods	EM (single particle)
Resolution	3.1 - 3.4 Å
Structure data	66146 9wpq EMDB-66146, PDB-9wpq: 5-HT2AR bound to LSD in complex with mini-Gq and scFv16 obtained by cryo-electron microscopy (cryoEM) Method: EM (single particle) / Resolution: 3.15 Å 66152 9wpx EMDB-66152, PDB-9wpx: 5-HT2AR bound to IHCH-1904 in complex with mini-Gq and scFv16 obtained by cryo-electron microscopy (cryoEM) Method: EM (single particle) / Resolution: 3.1 Å 66159 9wq5 EMDB-66159, PDB-9wq5: 5-HT2AR bound to IHCH-6122 in complex with mini-Gq and scFv16 obtained by cryo-electron microscopy (cryoEM) Method: EM (single particle) / Resolution: 3.2 Å 66160 9wq6 EMDB-66160, PDB-9wq6: 5-HT2AR bound to IHCH-1906 obtained by cryo-electron microscopy (cryoEM) Method: EM (single particle) / Resolution: 3.4 Å 66164 9wqa EMDB-66164, PDB-9wqa: 5-HT2B receptor bound to IHCH-1906 in complex with an antibody obtained by cryo-electron microscopy (cryoEM) Method: EM (single particle) / Resolution: 3.28 Å 66165 9wqb EMDB-66165, PDB-9wqb: 5-HT2B receptor bound to IHCH-6122 in complex with an antibody obtained by cryo-electron microscopy (cryoEM) Method: EM (single particle) / Resolution: 3.18 Å
Chemicals	ChemComp-7LD: (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide PDB-1eyi: FRUCTOSE-1,6-BISPHOSPHATASE COMPLEX WITH MAGNESIUM, FRUCTOSE-6-PHOSPHATE AND PHOSPHATE (R-STATE) PDB-1eyd: STRUCTURE OF WILD-TYPE S. NUCLEASE AT 1.7 A RESOLUTION PDB-1eye: 1.7 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF 6-HYDROXYMETHYL-7,8-DIHYDROPTEROATE SYNTHASE (DHPS) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH 6-HYDROXYMETHYLPTERIN MONOPHOSPHATE
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / serotonin receptor / membrane protein / 5-HT2AR / SIGNALING PROTEIN-IMMUNE SYSTEM complex