5YP5

Crystal structure of RORgamma complexed with SRC2 and compound 5d


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

From ROR gamma t Agonist to Two Types of ROR gamma t Inverse Agonists

Wang, Y.Cai, W.Tang, T.Liu, Q.Yang, T.Yang, L.Ma, Y.Zhang, G.Huang, Y.Song, X.Orband-Miller, L.A.Wu, Q.Zhou, L.Xiang, Z.Xiang, J.N.Leung, S.Shao, L.Lin, X.Lobera, M.Ren, F.

(2018) ACS Med Chem Lett 9: 120-124

  • DOI: https://doi.org/10.1021/acsmedchemlett.7b00476
  • Primary Citation of Related Structures:  
    5YP5, 5YP6

  • PubMed Abstract: 

    Biaryl amides as new RORγt modulators were discovered. The crystal structure of biaryl amide agonist 6 in complex with RORγt ligand binding domain (LBD) was resolved, and both "short" and "long" inverse agonists were obtained by removing from 6 or adding to 6 a proper structural moiety. While "short" inverse agonist ( 8 ) recruits a corepressor peptide and dispels a coactivator peptide, "long" inverse agonist ( 9 ) dispels both. The two types of inverse agonists can be utilized as potential tools to study mechanisms of Th17 transcriptional network inhibition and related disease biology.


  • Organizational Affiliation

    School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong, Shanghai 201203, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor ROR-gamma243Homo sapiensMutation(s): 0 
Gene Names: RORCNR1F3RORGRZRG
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
SRC2-2 peptide8Homo 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  
UniProt GroupQ15596
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4CZ
Query on 4CZ

Download Ideal Coordinates CCD File 
C [auth A]2-[4-(ethylsulfonyl)phenyl]-N-{5-[2-(2-methylpropyl)benzoyl]-4-phenyl-1,3-thiazol-2-yl}acetamide
C30 H30 N2 O4 S2
JCEZUYLHQPJLPN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4CZ BindingDB:  5YP5 IC50: 2.51e+4 (nM) from 1 assay(s)
EC50: 25 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.069α = 90
b = 62.069β = 90
c = 154.818γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data scaling
PHASERphasing
Cootmodel building

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-04-04
    Type: Initial release
  • Version 1.1: 2024-03-27
    Changes: Data collection, Database references