4UDC

GR in complex with dexamethasone


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.212 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Ligand Binding Mechanism in Steroid Receptors: From Conserved Plasticity to Differential Evolutionary Constraints.

Edman, K.Hosseini, A.Bjursell, M.K.Aagaard, A.Wissler, L.Gunnarsson, A.Kaminski, T.Kohler, C.Backstrom, S.Jensen, T.J.Cavallin, A.Karlsson, U.Nilsson, E.Lecina, D.Takahashi, R.Grebner, C.Geschwindner, S.Lepisto, M.Hogner, A.C.Guallar, V.

(2015) Structure 23: 2280

  • DOI: https://doi.org/10.1016/j.str.2015.09.012
  • Primary Citation of Related Structures:  
    4UDA, 4UDB, 4UDC, 4UDD

  • PubMed Abstract: 

    Steroid receptor drugs have been available for more than half a century, but details of the ligand binding mechanism have remained elusive. We solved X-ray structures of the glucocorticoid and mineralocorticoid receptors to identify a conserved plasticity at the helix 6-7 region that extends the ligand binding pocket toward the receptor surface. Since none of the endogenous ligands exploit this region, we hypothesized that it constitutes an integral part of the binding event. Extensive all-atom unbiased ligand exit and entrance simulations corroborate a ligand binding pathway that gives the observed structural plasticity a key functional role. Kinetic measurements reveal that the receptor residence time correlates with structural rearrangements observed in both structures and simulations. Ultimately, our findings reveal why nature has conserved the capacity to open up this region, and highlight how differences in the details of the ligand entry process result in differential evolutionary constraints across the steroid receptors.


  • Organizational Affiliation

    Discovery Sciences, AstraZeneca, Mölndal, Pepparedsleden 1, 43183 Mölndal, Sweden. Electronic address: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLUCOCORTICOID RECEPTOR280Homo sapiensMutation(s): 3 
UniProt & NIH Common Fund Data Resources
Find proteins for P04150 (Homo sapiens)
Explore P04150 
Go to UniProtKB:  P04150
PHAROS:  P04150
GTEx:  ENSG00000113580 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04150
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NUCLEAR RECEPTOR COACTIVATOR 214Homo sapiensMutation(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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CPS
Query on CPS

Download Ideal Coordinates CCD File 
C [auth A]3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE
C32 H58 N2 O7 S
UMCMPZBLKLEWAF-BCTGSCMUSA-N
DEX
Query on DEX

Download Ideal Coordinates CCD File 
D [auth A]DEXAMETHASONE
C22 H29 F O5
UREBDLICKHMUKA-CXSFZGCWSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DEX BindingDB:  4UDC Ki: min: 0.69, max: 6.8 (nM) from 9 assay(s)
Kd: min: 2, max: 19 (nM) from 3 assay(s)
IC50: min: 0.5, max: 22 (nM) from 33 assay(s)
EC50: min: 0.1, max: 30 (nM) from 22 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.212 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.66α = 90
b = 84.66β = 90
c = 105.91γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2015-11-25
    Type: Initial release
  • Version 1.1: 2015-12-09
    Changes: Database references
  • Version 1.2: 2015-12-16
    Changes: Database references
  • Version 1.3: 2019-04-03
    Changes: Data collection, Other, Source and taxonomy
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description