1KNU

LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.224 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity

Sauerberg, P.Pettersson, I.Jeppesen, L.Bury, P.S.Mogensen, J.P.Wassermann, K.Brand, C.L.Sturis, J.Woldike, H.F.Fleckner, J.Andersen, A.-S.T.Mortensen, S.B.Svensson, L.A.Rasmussen, H.B.Lehmann, S.V.Polivka, Z.Sindelar, K.Panajotova, V.Ynddal, L.Wulff, E.M.

(2002) J Med Chem 45: 789-804

  • DOI: https://doi.org/10.1021/jm010964g
  • Primary Citation of Related Structures:  
    1KNU

  • PubMed Abstract: 

    Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.


  • Organizational Affiliation

    Novo Nordisk A/S, Novo Nordisk Park E9 2.02, 2760 Måløv, Denmark. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA
A, B
274Homo sapiensMutation(s): 0 
Gene Names: PPARGNR1C3
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
YPA
Query on YPA

Download Ideal Coordinates CCD File 
C [auth A](S)-3-(4-(2-CARBAZOL-9-YL-ETHOXY)-PHENYL)-2-ETHOXY-PROPIONIC ACID
C25 H25 N O4
WUZIMDSVRIBNNI-DEOSSOPVSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
YPA BindingDB:  1KNU Kd: 170 (nM) from 1 assay(s)
EC50: 170 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.224 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.27α = 90
b = 63.44β = 101.84
c = 119.24γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
XDSdata reduction
CNXrefinement
CNXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-12-19
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Data collection, Refinement description
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description