2HWR

Structural basis for the structure-activity relationships of Peroxisome Proliferator-Activated Receptor agonists


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.34 Å
  • R-Value Free: 0.316 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.233 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists

Mahindroo, N.Peng, Y.H.Lin, C.H.Tan, U.K.Prakash, E.Lien, T.W.Lu, I.L.Lee, H.J.Hsu, J.T.A.Chen, X.Liao, C.C.Lyu, P.C.Chao, Y.S.Wu, S.Y.Hsieh, H.P.

(2006) J Med Chem 49: 6421-6424

  • DOI: https://doi.org/10.1021/jm060663c
  • Primary Citation of Related Structures:  
    2HWQ, 2HWR

  • PubMed Abstract: 

    Type 2 diabetes has rapidly reached an epidemic proportion becoming a major threat to global public health. PPAR agonists have emerged as a leading class of oral antidiabetic drugs. We report a structure biology analysis of novel indole-based PPAR agonists to explain the structure-activity relationships and present a critical analysis of reasons for change in selectivity with change in the orientation of the same scaffolds. The results would be helpful in designing novel PPAR agonists.


  • Organizational Affiliation

    Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peroxisome proliferator-activated receptor gamma
A, B
271Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P37231 (Homo sapiens)
Explore P37231 
Go to UniProtKB:  P37231
PHAROS:  P37231
GTEx:  ENSG00000132170 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP37231
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DRD
Query on DRD

Download Ideal Coordinates CCD File 
C [auth A]2-[(1-{3-[(6-BENZOYL-1-PROPYL-2-NAPHTHYL)OXY]PROPYL}-1H-INDOL-4-YL)OXY]-2-METHYLPROPANOIC ACID
C35 H35 N O5
PTLLEIWUBIYUFA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DRD BindingDB:  2HWR EC50: 210 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.34 Å
  • R-Value Free: 0.316 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.233 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.758α = 90
b = 89.775β = 90.32
c = 58.773γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-08-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description