3L0E

X-ray crystal structure of a Potent Liver X Receptor Modulator


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

Zuercher, W.J.Buckholz, R.G.Campobasso, N.Collins, J.L.Galardi, C.M.Gampe, R.T.Hyatt, S.M.Merrihew, S.L.Moore, J.T.Oplinger, J.A.Reid, P.R.Spearing, P.K.Stanley, T.B.Stewart, E.L.Willson, T.M.

(2010) J Med Chem 53: 3412-3416

  • DOI: https://doi.org/10.1021/jm901797p
  • Primary Citation of Related Structures:  
    3L0E

  • PubMed Abstract: 

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.


  • Organizational Affiliation

    GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. william.j.zuercher@gsk.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Oxysterols receptor LXR-beta253Homo sapiensMutation(s): 7 
Gene Names: NR1H2LXRBNERUNR
UniProt & NIH Common Fund Data Resources
Find proteins for P55055 (Homo sapiens)
Explore P55055 
Go to UniProtKB:  P55055
PHAROS:  P55055
GTEx:  ENSG00000131408 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55055
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor coactivator 212N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15596 (Homo sapiens)
Explore Q15596 
Go to UniProtKB:  Q15596
PHAROS:  Q15596
GTEx:  ENSG00000140396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15596
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
G58
Query on G58

Download Ideal Coordinates CCD File 
C [auth A]N-(2-chloro-6-fluorobenzyl)-1-methyl-N-{[3'-(methylsulfonyl)biphenyl-4-yl]methyl}-1H-imidazole-4-sulfonamide
C25 H23 Cl F N3 O4 S2
AYVVQXQFVKEXMX-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
G58 PDBBind:  3L0E IC50: 10 (nM) from 1 assay(s)
Binding MOAD:  3L0E IC50: 10 (nM) from 1 assay(s)
BindingDB:  3L0E IC50: 10 (nM) from 1 assay(s)
EC50: 79 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 41 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114.855α = 90
b = 114.855β = 90
c = 56.407γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-09-06
    Changes: Data collection, Refinement description