5TGZ

Crystal Structure of the Human Cannabinoid Receptor CB1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of the Human Cannabinoid Receptor CB1.

Hua, T.Vemuri, K.Pu, M.Qu, L.Han, G.W.Wu, Y.Zhao, S.Shui, W.Li, S.Korde, A.Laprairie, R.B.Stahl, E.L.Ho, J.H.Zvonok, N.Zhou, H.Kufareva, I.Wu, B.Zhao, Q.Hanson, M.A.Bohn, L.M.Makriyannis, A.Stevens, R.C.Liu, Z.J.

(2016) Cell 167: 750-762.e14

  • DOI: https://doi.org/10.1016/j.cell.2016.10.004
  • Primary Citation of Related Structures:  
    5TGZ

  • PubMed Abstract: 

    Cannabinoid receptor 1 (CB 1 ) is the principal target of Δ 9 -tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB 1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB 1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB 1 -AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB 1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB 1 and provides new opportunities for the design of next-generation CB 1 -targeting pharmaceuticals.


  • Organizational Affiliation

    iHuman Institute, ShanghaiTech University, Shanghai 201210, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cannabinoid receptor 1,Flavodoxin,Cannabinoid receptor 1452Homo sapiensNitratidesulfovibrio vulgaris str. HildenboroughMutation(s): 6 
Gene Names: CNR1CNRDVU_2680
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P00323 (Desulfovibrio vulgaris (strain ATCC 29579 / DSM 644 / NCIMB 8303 / VKM B-1760 / Hildenborough))
Explore P00323 
Go to UniProtKB:  P00323
Find proteins for P21554 (Homo sapiens)
Explore P21554 
Go to UniProtKB:  P21554
PHAROS:  P21554
GTEx:  ENSG00000118432 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00323P21554
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZDG
Query on ZDG

Download Ideal Coordinates CCD File 
B [auth A]4-[4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl]but-3-ynyl nitrate
C26 H25 Cl2 N5 O4
KXXKUWQMQUYUSE-UHFFFAOYSA-N
FMN
Query on FMN

Download Ideal Coordinates CCD File 
C [auth A]FLAVIN MONONUCLEOTIDE
C17 H21 N4 O9 P
FVTCRASFADXXNN-SCRDCRAPSA-N
OLC
Query on OLC

Download Ideal Coordinates CCD File 
D [auth A](2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-GDCKJWNLSA-N
OLA
Query on OLA

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A]
OLEIC ACID
C18 H34 O2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
H [auth A]DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.56α = 90
b = 52.63β = 111.14
c = 143.63γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-02
    Type: Initial release
  • Version 1.1: 2020-02-19
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description