1XLS

Crystal structure of the mouse CAR/RXR LBD heterodimer bound to TCPOBOP and 9cRA and a TIF2 peptide containg the third LXXLL motifs


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.96 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.255 

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This is version 1.5 of the entry. See complete history


Literature

The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.

Suino, K.Peng, L.Reynolds, R.Li, Y.Cha, J.Y.Repa, J.J.Kliewer, S.A.Xu, H.E.

(2004) Mol Cell 16: 893-905

  • DOI: https://doi.org/10.1016/j.molcel.2004.11.036
  • Primary Citation of Related Structures:  
    1XLS

  • PubMed Abstract: 

    Constitutive androstane receptor (CAR) induces xenobiotic, bilirubin, and thyroid hormone metabolism as a heterodimer with the retinoid X receptor (RXR). Unlike ligand-dependent nuclear receptors, CAR is constitutively active. Here, we report the heterodimeric structure of the CAR and RXR ligand binding domains (LBDs), which reveals an unusually large dimerization interface and a small CAR ligand binding pocket. Constitutive CAR activity appears to be mediated by the compact nature of the CAR LBD that displays several unique features including a shortened AF2 helix and helix H10, which are linked by a two-turn helix that normally adopts an extended loop in other receptors, and an extended helix H2 that stabilizes the canonical LBD fold by packing tightly against helix H3. These structural observations provide a molecular framework for understanding the atypical transcriptional activation properties of CAR.


  • Organizational Affiliation

    Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Retinoic acid receptor RXR-alpha
A, B, C, D
232Homo sapiensMutation(s): 0 
Gene Names: human
UniProt & NIH Common Fund Data Resources
Find proteins for P19793 (Homo sapiens)
Explore P19793 
Go to UniProtKB:  P19793
PHAROS:  P19793
GTEx:  ENSG00000186350 
Entity Groups  
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UniProt GroupP19793
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Orphan nuclear receptor NR1I3
E, F, G, H
242Mus musculusMutation(s): 0 
Gene Names: mouse
UniProt
Find proteins for O35627 (Mus musculus)
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Go to UniProtKB:  O35627
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UniProt GroupO35627
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor coactivator 2
I, J, K, L, M
I, J, K, L, M, N, O, P
18Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for Q9WUI9 (Rattus norvegicus)
Explore Q9WUI9 
Go to UniProtKB:  Q9WUI9
Entity Groups  
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UniProt GroupQ9WUI9
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
9CR BindingDB:  1XLS Ki: min: 3.8, max: 583 (nM) from 12 assay(s)
Kd: min: 1.5, max: 1810 (nM) from 19 assay(s)
IC50: min: 4, max: 82 (nM) from 5 assay(s)
EC50: min: 1.5, max: 316 (nM) from 22 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.96 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.255 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.271α = 79.02
b = 88.381β = 85.81
c = 105.494γ = 67.22
Software Package:
Software NamePurpose
CNSrefinement
MAR345data collection
SCALEPACKdata 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: 2004-12-28
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2016-11-09
    Changes: Non-polymer description, Source and taxonomy
  • Version 1.4: 2017-10-11
    Changes: Refinement description
  • Version 1.5: 2024-02-14
    Changes: Data collection, Database references, Derived calculations