4NB6

Crystal structure of the ligand binding domain of RORC with T0901317

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc.

Fauber, B.P., de Leon Boenig, G., Burton, B., Eidenschenk, C., Everett, C., Gobbi, A., Hymowitz, S.G., Johnson, A.R., Liimatta, M., Lockey, P., Norman, M., Ouyang, W., Rene, O., Wong, H.

(2013) Bioorg Med Chem Lett 23: 6604-6609

  • DOI: https://doi.org/10.1016/j.bmcl.2013.10.054
  • Primary Citation of Related Structures:  
    4NB6

  • PubMed Abstract: 

    The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.

    • Organizational Affiliation: 

    Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: Fauber.Benjamin@gene.com.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor ROR-gamma
A, B
251Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
444
Query on 444
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE
C17 H12 F9 N O3 S
SGIWFELWJPNFDH-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
444 BindingDB:  4NB6 Ki: 51 (nM) from 1 assay(s)
IC50: min: 60, max: 6500 (nM) from 12 assay(s)
EC50: min: 54, max: 463 (nM) from 4 assay(s)
PDBBind:  4NB6 IC50: 60 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.222 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.534α = 90
b = 99.534β = 90
c = 125.777γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-27
    Type: Initial release
  • Version 1.1: 2013-12-18
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description