2QTU

Estrogen receptor beta ligand-binding domain complexed to a benzopyran ligand


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.53 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.264 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 5: Combined A- and C-ring structure-activity relationship studies.

Richardson, T.I.Dodge, J.A.Wang, Y.Durbin, J.D.Krishnan, V.Norman, B.H.

(2007) Bioorg Med Chem Lett 17: 5563-5566

  • DOI: https://doi.org/10.1016/j.bmcl.2007.08.009
  • Primary Citation of Related Structures:  
    2QTU

  • PubMed Abstract: 

    Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the synthesis of a late stage intermediate that allowed us to combine A-ring and C-ring modifications and carry out simultaneous SAR studies at both positions. Modification of both positions proved additive, maintaining affinity and improving ERbeta selectivity up to 83-fold. An X-ray cocrystal structure confirms the previously observed binding mode in ERbeta.


  • Organizational Affiliation

    Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. t_richardson@lilly.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen receptor beta
A, B
257Homo sapiensMutation(s): 0 
Gene Names: ESR2ESTRBNR3A2
UniProt & NIH Common Fund Data Resources
Find proteins for Q92731 (Homo sapiens)
Explore Q92731 
Go to UniProtKB:  Q92731
PHAROS:  Q92731
GTEx:  ENSG00000140009 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ92731
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3AS
Query on 3AS

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(3aS,4R,9bR)-2,2-difluoro-4-(4-hydroxyphenyl)-6-(methoxymethyl)-1,2,3,3a,4,9b-hexahydrocyclopenta[c]chromen-8-ol
C20 H20 F2 O4
GPFRMIHXGMVMGF-BZSNNMDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3AS PDBBind:  2QTU Ki: 0.53 (nM) from 1 assay(s)
BindingDB:  2QTU Ki: 0.53 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.53 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.264 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.798α = 90
b = 63.798β = 90
c = 249.616γ = 120
Software Package:
Software NamePurpose
CNXrefinement
MAR345dtbdata collection
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations