[English] 日本語
Yorodumi
- EMDB-76463: Locally refined cryo-EM structure of human cannabinoid receptor 2... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-76463
TitleLocally refined cryo-EM structure of human cannabinoid receptor 2 with agonist '5249
Map data
Sample
  • Complex: Human cannabinoid receptor 2 with agonist '5249
    • Protein or peptide: Cannabinoid receptor 2
  • Ligand: (3R)-3-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]ethyl}-2-benzofuran-1(3H)-one
KeywordsHuman cannabinoid receptor 2 / CNR2 / CB2 receptor / Gi1 / Agonist-bound state / AM12435-bound complex / Active-state GPCR / Class A rhodopsin-like receptor / Cryo-electron microscopy structure / MEMBRANE PROTEIN
Function / homology
Function and homology information


trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / negative regulation of mast cell activation / negative regulation of synaptic transmission, GABAergic / cannabinoid receptor activity / negative regulation of action potential / Class A/1 (Rhodopsin-like receptors) / extrinsic component of cytoplasmic side of plasma membrane / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / response to amphetamine / adenylate cyclase-activating G protein-coupled receptor signaling pathway ...trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / negative regulation of mast cell activation / negative regulation of synaptic transmission, GABAergic / cannabinoid receptor activity / negative regulation of action potential / Class A/1 (Rhodopsin-like receptors) / extrinsic component of cytoplasmic side of plasma membrane / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / response to amphetamine / adenylate cyclase-activating G protein-coupled receptor signaling pathway / response to lipopolysaccharide / G alpha (i) signalling events / response to ethanol / perikaryon / postsynaptic membrane / immune response / inflammatory response / dendrite / endoplasmic reticulum / plasma membrane / cytoplasm
Similarity search - Function
Cannabinoid receptor type 2 / Cannabinoid receptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile.
Similarity search - Domain/homology
Cannabinoid receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.94 Å
AuthorsSacco M / Wu C / Singal B / Skiniotis G
Funding support United States, 1 items
OrganizationGrant numberCountry
Defense Advanced Research Projects Agency (DARPA) United States
CitationJournal: J Med Chem / Year: 2026
Title: Library Docking for Cannabinoid-2 Receptor Ligands.
Authors: Moira M Rachman / Christos Iliopoulos-Tsoutsouvas / Michael D Sacco / Xinyu Xu / Cheng-Guo Wu / Emma Santos / Isabella S Glenn / Lu Paris / Michelle K Cahill / Suthakar Ganapathy / Tia A ...Authors: Moira M Rachman / Christos Iliopoulos-Tsoutsouvas / Michael D Sacco / Xinyu Xu / Cheng-Guo Wu / Emma Santos / Isabella S Glenn / Lu Paris / Michelle K Cahill / Suthakar Ganapathy / Tia A Tummino / Yurii S Moroz / Dmytro S Radchenko / Meri Okorie / Vivianne L Tawfik / John J Irwin / Alexandros Makriyannis / Georgios Skiniotis / Brian K Shoichet /
Abstract: Cannabinoid receptors are both therapeutically attractive and are interesting model systems for structure-based methods. Here we investigated topical questions in library docking using the CB2 ...Cannabinoid receptors are both therapeutically attractive and are interesting model systems for structure-based methods. Here we investigated topical questions in library docking using the CB2 receptor. While a CB1R docking campaign found potent but nonselective ligands, here subtype selective ligands were found by targeting polar residues. Hit rates and hit affinities improved with library size, but docking against active and inactive receptor states did not reliably bias toward agonists or antagonists. Cryo-EM structures of two of the new agonists superposed well on the docking predictions. Structure-based optimization led to 10- to 140-fold improvements within three series, consistent with well-behaved ligands. Hit rates with an explicit 2.6 billion molecule library resembled those of an implied 11 billion molecule library from a building-block method, supporting the latter's ability to explore this space, though higher affinities were discovered from the explicit set. Implications for future studies are considered.
History
DepositionApr 7, 2026-
Header (metadata) releaseJul 15, 2026-
Map releaseJul 15, 2026-
UpdateJul 15, 2026-
Current statusJul 15, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_76463.png

Downloads & links

-
Map

FileDownload / File: emd_76463.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.92 Å/pix.
x 256 pix.
= 235.52 Å		0.92 Å/pix.
x 256 pix.
= 235.52 Å		0.92 Å/pix.
x 256 pix.
= 235.52 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.92 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.105
Minimum - Maximum-0.2201799 - 0.48398888
Average (Standard dev.)-0.00085723697 (±0.011995285)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 235.52 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_76463_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_76463_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human cannabinoid receptor 2 with agonist '5249

EntireName: Human cannabinoid receptor 2 with agonist '5249
Components
  • Complex: Human cannabinoid receptor 2 with agonist '5249
    • Protein or peptide: Cannabinoid receptor 2
  • Ligand: (3R)-3-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]ethyl}-2-benzofuran-1(3H)-one

-
Supramolecule #1: Human cannabinoid receptor 2 with agonist '5249

SupramoleculeName: Human cannabinoid receptor 2 with agonist '5249 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Cannabinoid receptor 2

MacromoleculeName: Cannabinoid receptor 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 41.442398 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DYKDDDDENL YFQGMEECWV TEIANGSKDG LDSNPMKDYM ILSGPQKTAV AVLCTLLGLL SALENVAVLY LILSSHQLRR KPSYLFIGS LAGADFLASV VFACSFVNFH VFHGVDSKAV FLLKIGSVTM TFTASVGSLL LTAIDRYLCL RYPPSYKALL T RGRALVTL ...String:
DYKDDDDENL YFQGMEECWV TEIANGSKDG LDSNPMKDYM ILSGPQKTAV AVLCTLLGLL SALENVAVLY LILSSHQLRR KPSYLFIGS LAGADFLASV VFACSFVNFH VFHGVDSKAV FLLKIGSVTM TFTASVGSLL LTAIDRYLCL RYPPSYKALL T RGRALVTL GIMWVLSALV SYLPLMGWTC CPRPCSELFP LIPNDYLLSW LLFIAFLFSG IIYTYGHVLW KAHQHVASLS GH QDRQVPG MARMRLDVRL AKTLGLVLAV LLICWFPVLA LMAHSLATTL SDQVKKAFAF CSMLCLINSM VNPVIYALRS GEI RSSAHH CLAHWKKCVR GLGSEAKEEA PRSSVTETEA DGKITPWPDS RDLDLSDC

UniProtKB: Cannabinoid receptor 2

-
Macromolecule #2: (3R)-3-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydro-1,5-benzoxazepin...

MacromoleculeName: (3R)-3-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]ethyl}-2-benzofuran-1(3H)-one
type: ligand / ID: 2 / Number of copies: 1 / Formula: A1DB5
Molecular weightTheoretical: 391.341 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration5 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.4 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 8390158
Details: After patch motion correction and patch CTF estimation
CTF correctionSoftware - Name: cryoSPARC
Details: CTF parameters estimated using Patch CTF in cryoSPARC. Phase and amplitude corrections applied during reconstruction and refinement.
Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6kpf

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 505644
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
FSC plot (resolution estimation)

+
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