4OO9

Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.239 
  • R-Value Observed: 0.241 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain.

Dore, A.S.Okrasa, K.Patel, J.C.Serrano-Vega, M.Bennett, K.Cooke, R.M.Errey, J.C.Jazayeri, A.Khan, S.Tehan, B.Weir, M.Wiggin, G.R.Marshall, F.H.

(2014) Nature 511: 557-562

  • DOI: https://doi.org/10.1038/nature13396
  • Primary Citation of Related Structures:  
    4OO9

  • PubMed Abstract: 

    Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmembrane domain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class C G-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders.


  • Organizational Affiliation

    1] Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK [2].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Metabotropic glutamate receptor 5, Lysozyme, Metabotropic glutamate receptor 5 chimera444Homo sapiensTequatrovirus T4Mutation(s): 8 
Gene Names: GRM5GPRC1EMGLUR5E
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P41594 (Homo sapiens)
Explore P41594 
Go to UniProtKB:  P41594
PHAROS:  P41594
GTEx:  ENSG00000168959 
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP41594P00720
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
YCM
Query on YCM
A
L-PEPTIDE LINKINGC5 H10 N2 O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
2U8 BindingDB:  4OO9 Ki: min: 5.6, max: 10 (nM) from 2 assay(s)
IC50: min: 10, max: 72 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.239 
  • R-Value Observed: 0.241 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.242α = 90
b = 43.555β = 99.37
c = 82.049γ = 90
Software Package:
Software NamePurpose
GDAdata collection
PHASERphasing
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2014-07-02
    Type: Initial release
  • Version 1.1: 2014-07-09
    Changes: Database references
  • Version 1.2: 2014-07-16
    Changes: Atomic model, Non-polymer description, Source and taxonomy, Structure summary
  • Version 1.3: 2014-08-06
    Changes: Database references
  • Version 1.4: 2015-07-15
    Changes: Source and taxonomy
  • Version 1.5: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.6: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description