4N73

Crystal structure of the ligand binding domain (LBD) of REV-ERB beta bound to Cobalt Protoporphyrin IX


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.87 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure of REV-ERB beta Ligand-binding Domain Bound to a Porphyrin Antagonist.

Matta-Camacho, E.Banerjee, S.Hughes, T.S.Solt, L.A.Wang, Y.Burris, T.P.Kojetin, D.J.

(2014) J Biol Chem 289: 20054-20066

  • DOI: https://doi.org/10.1074/jbc.M113.545111
  • Primary Citation of Related Structures:  
    4N73

  • PubMed Abstract: 

    REV-ERBα and REV-ERBβ are members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors that play important roles in the regulation of circadian physiology, metabolism, and immune function. Although the REV-ERBs were originally characterized as orphan receptors, recent studies have demonstrated that they function as receptors for heme. Here, we demonstrate that cobalt protoporphyrin IX (CoPP) and zinc protoporphyrin IX (ZnPP) are ligands that bind directly to the REV-ERBs. However, instead of mimicking the agonist action of heme, CoPP and ZnPP function as antagonists of REV-ERB function. This was unexpected because the only distinction between these ligands is the metal ion that is coordinated. To understand the structural basis by which REV-ERBβ can differentiate between a porphyrin agonist and antagonist, we characterized the interaction between REV-ERBβ with heme, CoPP, and ZnPP using biochemical and structural approaches, including x-ray crystallography and NMR. The crystal structure of CoPP-bound REV-ERBβ indicates only minor conformational changes induced by CoPP compared with heme, including the porphyrin ring of CoPP, which adopts a planar conformation as opposed to the puckered conformation observed in the heme-bound REV-ERBβ crystal structure. Thus, subtle changes in the porphyrin metal center and ring conformation may influence the agonist versus antagonist action of porphyrins and when considered with other studies suggest that gas binding to the iron metal center heme may drive alterations in REV-ERB activity.


  • Organizational Affiliation

    From the Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33418 and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor subfamily 1 group D member 2199Homo sapiensMutation(s): 1 
Gene Names: NR1D2R1D2
UniProt & NIH Common Fund Data Resources
Find proteins for Q14995 (Homo sapiens)
Explore Q14995 
Go to UniProtKB:  Q14995
PHAROS:  Q14995
GTEx:  ENSG00000174738 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14995
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
COH
Query on COH

Download Ideal Coordinates CCD File 
B [auth A]PROTOPORPHYRIN IX CONTAINING CO
C34 H32 Co N4 O4
AQTFKGDWFRRIHR-RGGAHWMASA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.87 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.66α = 90
b = 48.68β = 90
c = 69.75γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-06-04
    Type: Initial release
  • Version 1.1: 2014-07-02
    Changes: Database references
  • Version 1.2: 2014-07-30
    Changes: Database references
  • Version 1.3: 2018-03-14
    Changes: Database references
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description