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Open data
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Basic information
Entry | Database: PDB / ID: 8cc7 | ||||||
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Title | Mouse serotonin 5-HT3A receptor in complex with PZ-1939 | ||||||
![]() | 5-hydroxytryptamine receptor 3A | ||||||
![]() | TRANSPORT PROTEIN / Ion channel / Receptor / pLGIC | ||||||
Function / homology | ![]() Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / cleavage furrow / transmembrane transporter complex / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / cleavage furrow / transmembrane transporter complex / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / presynaptic membrane / postsynaptic membrane / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
![]() | Lopez-Sanchez, U. / Nury, H. | ||||||
Funding support | European Union, 1items
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![]() | ![]() Title: Superiority of the Triple-Acting 5-HTR/5-HTR Antagonist and MAO-B Reversible Inhibitor over 5-HTR Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats. Authors: Katarzyna Grychowska / Uriel López-Sánchez / Mathieu Vitalis / Geoffrey Canet / Grzegorz Satała / Agnieszka Olejarz-Maciej / Joanna Gołębiowska / Rafał Kurczab / Wojciech Pietruś / ...Authors: Katarzyna Grychowska / Uriel López-Sánchez / Mathieu Vitalis / Geoffrey Canet / Grzegorz Satała / Agnieszka Olejarz-Maciej / Joanna Gołębiowska / Rafał Kurczab / Wojciech Pietruś / Monika Kubacka / Christophe Moreau / Maria Walczak / Klaudia Blicharz-Futera / Ophélie Bento / Xavier Bantreil / Gilles Subra / Andrzej J Bojarski / Frédéric Lamaty / Carine Becamel / Charleine Zussy / Séverine Chaumont-Dubel / Piotr Popik / Hugues Nury / Philippe Marin / Laurent Givalois / Paweł Zajdel / ![]() ![]() ![]() Abstract: The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets ...The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD. The key structural features required for MAO-B inhibition and 5-HTR antagonism and interaction with 5-HTR were determined using molecular dynamic simulations and cryo-electron microscopy, respectively. Bioavailable reversed scopolamine-induced cognitive deficits in the novel object recognition test. Furthermore, it displayed superior pro-cognitive properties compared to intepirdine (a 5-HTR antagonist) in the AD model, which involved intracerebroventricular injection of an oligomeric solution of amyloid-β peptide (oAβ) in the T-maze test in rats. , but not intepirdine, restored levels of biomarkers characteristic of the debilitating effects of oAβ. These data support the potential of a multitarget approach involving the joint modulation of 5-HTR/5-HTR/MAO-B in AD. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 424.4 KB | Display | ![]() |
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PDB format | ![]() | 342.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 16557MC ![]() 8cc6C 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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1 |
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Components
#1: Protein | Mass: 63682.719 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Sugar | ChemComp-NAG / #4: Chemical | ChemComp-U9Q / Has ligand of interest | Y | |
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-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: Mouse serotonin 5-HT3A receptor in complex with PZ-1922 Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
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 |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2300 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 102137 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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