3O6I

Ligand-binding domain of GluA2 (flip) ionotropic glutamate receptor in complex with an allosteric modulator

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

A novel series of positive modulators of the AMPA receptor: structure-based lead optimization.

Jamieson, C., Campbell, R.A., Cumming, I.A., Gillen, K.J., Gillespie, J., Kazemier, B., Kiczun, M., Lamont, Y., Lyons, A.J., Maclean, J.K., Martin, F., Moir, E.M., Morrow, J.A., Pantling, J., Rankovic, Z., Smith, L.

(2010) Bioorg Med Chem Lett 20: 6072-6075

  • DOI: https://doi.org/10.1016/j.bmcl.2010.08.063
  • Primary Citation of Related Structures:  
    3O6G, 3O6H, 3O6I

  • PubMed Abstract: 

    Starting from lead compound 1, we demonstrate how X-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity.

    • Organizational Affiliation: 

    Merck Research Laboratories, MSD, Newhouse, Motherwell, Lanarkshire, UK. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutamate receptor 2263Rattus norvegicusMutation(s): 0 
Gene Names: Gria2, Glur2
UniProt
Find proteins for P19491 (Rattus norvegicus)
Explore P19491 
Go to UniProtKB:  P19491
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19491
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
O26
Query on O26
Download Ideal Coordinates CCD File 
C [auth A]2-[({3-tert-butyl-4-[(methylamino)methyl]-1H-pyrazol-1-yl}acetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
C20 H29 N5 O2 S
ORJNBGRVTFLPLF-UHFFFAOYSA-N
GLU
Query on GLU
Download Ideal Coordinates CCD File 
B [auth A]GLUTAMIC ACID
C5 H9 N O4
WHUUTDBJXJRKMK-VKHMYHEASA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A]		SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.24α = 90
b = 87.8β = 90
c = 47.38γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
AMoREphasing
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-15
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-08-09
    Changes: Refinement description, Source and taxonomy