4NIE

Crystal structure of the orphan nuclear receptor ROR(gamma)t ligand-binding domain in complex with small molecule ligand

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.01 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

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This is version 1.3 of the entry. See complete history. 


Literature

Discovery of Tertiary Amine and Indole Derivatives as Potent ROR gamma t Inverse Agonists.

Yang, T., Liu, Q., Cheng, Y., Cai, W., Ma, Y., Yang, L., Wu, Q., Orband-Miller, L.A., Zhou, L., Xiang, Z., Huxdorf, M., Zhang, W., Zhang, J., Xiang, J.N., Leung, S., Qiu, Y., Zhong, Z., Elliott, J.D., Lin, X., Wang, Y.

(2014) ACS Med Chem Lett 5: 65-68

  • DOI: https://doi.org/10.1021/ml4003875
  • Primary Citation of Related Structures:  
    4NIE

  • PubMed Abstract: 

    A novel series of tertiary amines as retinoid-related orphan receptor gamma-t (RORγt) inverse agonists was discovered through agonist/inverse agonist conversion. The level of RORγt inhibition can be enhanced by modulating the conformational disruption of H12 in RORγt LBD. Linker exploration and rational design led to the discovery of more potent indole-based RORγt inverse agonists.

    • Organizational Affiliation: 

    Research and Development, GlaxoSmithKline , No. 3 Building, 898 Halei Road, Pudong, Shanghai 201203, China.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor ROR-gamma
A, B
262Homo sapiensMutation(s): 0 
Gene Names: NR1F3, RORC, RORG, RZRG
UniProt & NIH Common Fund Data Resources
Find proteins for P51449 (Homo sapiens)
Explore P51449 
Go to UniProtKB:  P51449
PHAROS:  P51449
GTEx:  ENSG00000143365 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP51449
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide from Nuclear receptor coactivator 2
C, D
12Homo 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
Binding Affinity Annotations 
IDSourceBinding Affinity
NBH PDBBind:  4NIE IC50: 20 (nM) from 1 assay(s)
BindingDB:  4NIE IC50: 2.50e+4 (nM) from 1 assay(s)
EC50: min: 7.8, max: 110 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.01 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.085α = 90
b = 86.349β = 90
c = 91.98γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-11
    Type: Initial release
  • Version 1.1: 2017-10-04
    Changes: Data collection
  • Version 1.2: 2019-12-25
    Changes: Database references
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references, Derived calculations