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- PDB-9bsb: Global reconstruction of DRD2 bound to LSD in complex with a mini... -
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Basic information
Entry | Database: PDB / ID: 9bsb | ||||||||||||||||||||||||
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Title | Global reconstruction of DRD2 bound to LSD in complex with a mini-GoA and scFv16 obtained by cryo-electron microscopy (cryoEM) | ||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / GPCR / G-protein Coupled Receptor / DRD2 / serotonin / psychedelics | ||||||||||||||||||||||||
Function / homology | ![]() negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / response to histamine / regulation of synapse structural plasticity ...negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / response to histamine / regulation of synapse structural plasticity / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / adenohypophysis development / negative regulation of dopamine secretion / positive regulation of renal sodium excretion / negative regulation of cellular response to hypoxia / hyaloid vascular plexus regression / adenylate cyclase-inhibiting dopamine receptor signaling pathway / response to inactivity / regulation of potassium ion transport / orbitofrontal cortex development / cerebral cortex GABAergic interneuron migration / Dopamine receptors / negative regulation of neuron migration / dopamine binding / branching morphogenesis of a nerve / regulation of dopamine uptake involved in synaptic transmission / positive regulation of growth hormone secretion / phospholipase C-activating dopamine receptor signaling pathway / peristalsis / heterotrimeric G-protein binding / drinking behavior / G protein-coupled receptor complex / grooming behavior / behavioral response to ethanol / auditory behavior / positive regulation of G protein-coupled receptor signaling pathway / mu-type opioid receptor binding / striatum development / corticotropin-releasing hormone receptor 1 binding / dopaminergic synapse / positive regulation of urine volume / positive regulation of multicellular organism growth / G protein-coupled receptor internalization / non-motile cilium / vesicle docking involved in exocytosis / negative regulation of synaptic transmission, glutamatergic / heterocyclic compound binding / response to iron ion / adult walking behavior / G protein-coupled dopamine receptor signaling pathway / arachidonate secretion / response to morphine / ciliary membrane / negative regulation of cytosolic calcium ion concentration / regulation of synaptic transmission, GABAergic / temperature homeostasis / positive regulation of neuroblast proliferation / pigmentation / regulation of heart contraction / positive regulation of cytokinesis / parallel fiber to Purkinje cell synapse / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / dopamine metabolic process / cellular response to ethanol / response to light stimulus / associative learning / positive regulation of receptor internalization / lateral plasma membrane / endocytic vesicle / G-protein alpha-subunit binding / neuroblast proliferation / negative regulation of protein secretion / long-term memory / potassium channel regulator activity / sperm flagellum / prepulse inhibition / postsynaptic modulation of chemical synaptic transmission / response to axon injury / behavioral response to cocaine / regulation of sodium ion transport / synapse assembly / negative regulation of blood pressure / cellular response to retinoic acid / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / release of sequestered calcium ion into cytosol / axon terminus / ionotropic glutamate receptor binding / presynaptic modulation of chemical synaptic transmission / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / acrosomal vesicle / axonogenesis / muscle contraction / regulation of heart rate / negative regulation of innate immune response / negative regulation of cell migration / response to amphetamine Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.32 Å | ||||||||||||||||||||||||
![]() | Kim, K. / Gumpper, R.H. / Fay, J.F. / Roth, B.L. | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Authors: Manish K Jain / Ryan H Gumpper / Samuel T Slocum / Gavin P Schmitz / Jakob S Madsen / Tia A Tummino / Carl-Mikael Suomivuori / Xi-Ping Huang / Laura Shub / Jeffrey F DiBerto / Kuglae Kim / ...Authors: Manish K Jain / Ryan H Gumpper / Samuel T Slocum / Gavin P Schmitz / Jakob S Madsen / Tia A Tummino / Carl-Mikael Suomivuori / Xi-Ping Huang / Laura Shub / Jeffrey F DiBerto / Kuglae Kim / Chelsea DeLeon / Brain E Krumm / Jonathan F Fay / Michael Keiser / Alexander S Hauser / Ron O Dror / Brian Shoichet / David E Gloriam / David E Nichols / Bryan L Roth / ![]() ![]() ![]() Abstract: The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT serotonin receptor (5-HTR). Recent clinical ...The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT serotonin receptor (5-HTR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety, migraine and cluster headaches, drug abuse, and post-traumatic stress disorder. In this study, we investigated the pharmacology of 41 classical psychedelics from the tryptamine, phenethylamine, and lysergamide chemical classes. We profiled these compounds against 318 human G-protein-coupled receptors (GPCRs) to elucidate their target profiles, and in the case of LSD, against more than 450 human kinases. We found that psychedelics have potent and efficacious actions at nearly every serotonin, dopamine, and adrenergic receptor. We quantified their activation for multiple transducers and found that psychedelics stimulate multiple 5-HTR transducers, each of which correlates with psychedelic drug-like actions in vivo. Our results suggest that multiple molecular targets likely contribute to the actions of psychedelics. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 231.1 KB | Display | ![]() |
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PDB format | ![]() | 169.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 39 KB | Display | |
Data in CIF | ![]() | 59.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 44866MC ![]() 9bs9C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BCA
#1: Protein | Mass: 38146.707 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Protein | Mass: 40221.570 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RE

#3: Protein | Mass: 67234.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: cybC, DRD2 / Production host: ![]() ![]() |
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#4: Antibody | Mass: 28674.902 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#6: Chemical | ChemComp-7LD / ( |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: DRD2 in complex mini-GoA / Type: COMPLEX / Entity ID: #3, #1-#2, #4-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER / Nominal defocus max: 2600 nm / Nominal defocus min: 170 nm |
Image recording | Electron dose: 49.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.32 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2485527 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 2.32 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
Refine LS restraints |
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