[English] 日本語
Yorodumi
- PDB-7vod: Crystal structure of 5-HT2AR in complex with cariprazine -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7vod
TitleCrystal structure of 5-HT2AR in complex with cariprazine
Components5-hydroxytryptamine receptor 2A,Soluble cytochrome b562
KeywordsMEMBRANE PROTEIN / GPCR / Dopamine Receptor / serotonin receptor / cariprazine / antipsychotic
Function / homology
Function and homology information


protein localization to cytoskeleton / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / artery smooth muscle contraction / serotonin receptor signaling pathway / Serotonin receptors ...protein localization to cytoskeleton / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / artery smooth muscle contraction / serotonin receptor signaling pathway / Serotonin receptors / cell body fiber / urinary bladder smooth muscle contraction / serotonin binding / negative regulation of synaptic transmission, glutamatergic / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / temperature homeostasis / regulation of dopamine secretion / protein tyrosine kinase activator activity / behavioral response to cocaine / detection of temperature stimulus involved in sensory perception of pain / negative regulation of potassium ion transport / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / : / positive regulation of fat cell differentiation / detection of mechanical stimulus involved in sensory perception of pain / release of sequestered calcium ion into cytosol / positive regulation of vasoconstriction / presynaptic modulation of chemical synaptic transmission / positive regulation of glycolytic process / phosphatidylinositol 3-kinase/protein kinase B signal transduction / dendritic shaft / caveola / electron transport chain / glycolytic process / memory / intracellular calcium ion homeostasis / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of neuron apoptotic process / virus receptor activity / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / G alpha (q) signalling events / chemical synaptic transmission / postsynaptic membrane / periplasmic space / electron transfer activity / positive regulation of ERK1 and ERK2 cascade / response to xenobiotic stimulus / iron ion binding / axon / neuronal cell body / glutamatergic synapse / dendrite / heme binding / positive regulation of cell population proliferation / protein-containing complex binding / identical protein binding / plasma membrane
Similarity search - Function
5-Hydroxytryptamine 2A receptor / 5-hydroxytryptamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
Chem-7RU / CHOLESTEROL / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / Soluble cytochrome b562 / 5-hydroxytryptamine receptor 2A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.3 Å
AuthorsChen, Z. / Fan, L. / Wang, H. / Yu, J. / Lu, D. / Qi, J. / Nie, F. / Luo, Z. / Liu, Z. / Cheng, J. / Wang, S.
Funding support China, 3items
OrganizationGrant numberCountry
Chinese Academy of SciencesXDB19020111 China
Ministry of Science and Technology (MoST, China)2020YFA0509600 China
National Natural Science Foundation of China (NSFC)32071197 China
CitationJournal: Nat.Neurosci. / Year: 2022
Title: Structure-based design of a novel third-generation antipsychotic drug lead with potential antidepressant properties.
Authors: Chen, Z. / Fan, L. / Wang, H. / Yu, J. / Lu, D. / Qi, J. / Nie, F. / Luo, Z. / Liu, Z. / Cheng, J. / Wang, S.
History
DepositionOct 13, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 22, 2021Provider: repository / Type: Initial release
Revision 1.1Dec 29, 2021Group: Data collection / Structure summary / Category: diffrn / entity / Item: _diffrn.ambient_temp / _entity.pdbx_mutation
Revision 1.2Feb 16, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID
Revision 1.3Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 5-hydroxytryptamine receptor 2A,Soluble cytochrome b562
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,6399
Polymers41,9581
Non-polymers2,6818
Water0
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area270 Å2
ΔGint-2 kcal/mol
Surface area18490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)50.270, 55.040, 180.290
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21221
Components on special symmetry positions
IDModelComponents
11A-1201-

MG

-
Components

#1: Protein 5-hydroxytryptamine receptor 2A,Soluble cytochrome b562 / 5-HT-2 / 5-HT-2A / Serotonin receptor 2A / Cytochrome b-562


Mass: 41958.074 Da / Num. of mol.: 1 / Mutation: S162K,N164W,M1007W,R1098I,H1102I,R1106G,S372N
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HTR2A, HTR2, cybC / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P28223, UniProt: P0ABE7
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#3: Chemical ChemComp-CLR / CHOLESTEROL / Cholesterol


Mass: 386.654 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C27H46O
#4: Chemical ChemComp-OLC / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / 1-Oleoyl-R-glycerol


Mass: 356.540 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C21H40O4
#5: Chemical ChemComp-7RU / 3-[4-[2-[4-[2,3-bis(chloranyl)phenyl]piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethyl-urea / Cariprazine / Cariprazine


Mass: 427.411 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H32Cl2N4O / Feature type: SUBJECT OF INVESTIGATION / Comment: antipsychotic, agonist*YM
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.97 Å3/Da / Density % sol: 58.62 %
Crystal growTemperature: 293.15 K / Method: lipidic cubic phase / Details: 100 mM Tris/HCl, 100 mM Potassium formate, 30% PEG / PH range: 6.5-7.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL45XU / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 6, 2020
RadiationMonochromator: M / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.3→48.42 Å / Num. obs: 7889 / % possible obs: 97.8 % / Redundancy: 14.2 % / CC1/2: 0.999 / Rmerge(I) obs: 0.273 / Rpim(I) all: 0.072 / Rrim(I) all: 0.283 / Net I/σ(I): 8.1
Reflection shellResolution: 3.3→3.56 Å / Redundancy: 6.8 % / Rmerge(I) obs: 1.25 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 1449 / CC1/2: 0.396 / Rpim(I) all: 0.472 / Rrim(I) all: 1.35 / % possible all: 89.6

-
Processing

Software
NameVersionClassification
PHENIX1.12-2829-000refinement
XSCALEdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6A93

6a93


Resolution: 3.3→48.42 Å / Cor.coef. Fo:Fc: 0.891 / Cor.coef. Fo:Fc free: 0.924 / SU B: 28.929 / SU ML: 0.437 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.5 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.239 381 4.8 %RANDOM
Rwork0.2176 ---
obs0.2187 7475 97.69 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 220.53 Å2 / Biso mean: 77.625 Å2 / Biso min: 11.73 Å2
Baniso -1Baniso -2Baniso -3
1-1.67 Å20 Å2-0 Å2
2--4.89 Å20 Å2
3----6.57 Å2
Refinement stepCycle: final / Resolution: 3.3→48.42 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2711 0 155 0 2866
Biso mean--108.83 --
Num. residues----355
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0132924
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172874
X-RAY DIFFRACTIONr_angle_refined_deg1.8771.6453985
X-RAY DIFFRACTIONr_angle_other_deg1.7541.616632
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.4445350
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.86423.704108
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.05715459
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.304156
X-RAY DIFFRACTIONr_chiral_restr0.0860.2419
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.023069
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02566
X-RAY DIFFRACTIONr_mcbond_it8.3037.941415
X-RAY DIFFRACTIONr_mcbond_other8.3027.9381414
X-RAY DIFFRACTIONr_mcangle_it12.36511.8961760
LS refinement shellResolution: 3.3→3.385 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.373 28 -
Rwork0.351 456 -
all-484 -
obs--82.17 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more