5LSG

PPARgamma complex with the betulinic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.229 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Betulinic acid is a PPAR gamma antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis.

Brusotti, G.Montanari, R.Capelli, D.Cattaneo, G.Laghezza, A.Tortorella, P.Loiodice, F.Peiretti, F.Bonardo, B.Paiardini, A.Calleri, E.Pochetti, G.

(2017) Sci Rep 7: 5777-5777

  • DOI: https://doi.org/10.1038/s41598-017-05666-6
  • Primary Citation of Related Structures:  
    5LSG

  • PubMed Abstract: 

    PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for metabolic diseases. In this work, an affinity-based bioassay was found to be effective for selecting PPAR ligands from the dried extract of an African plant (Diospyros bipindensis). Among the ligands, we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARγ and PPARα antagonist. Cell differentiation assays showed that BA inhibits adipogenesis and promotes osteogenesis; either down-regulates or does not affect the expression of a series of adipogenic markers; and up-regulates the expression of osteogenic markers. Moreover, BA increases basal glucose uptake in 3T3-L1 adipocytes. The crystal structure of the complex of BA with PPARγ sheds light, at the molecular level, on the mechanism by which BA antagonizes PPARγ, and indicates a unique binding mode of this antagonist type. The results of this study show that the natural compound BA could be an interesting and safe candidate for the treatment of type 2 diabetes and bone diseases.


  • Organizational Affiliation

    Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, Via Taramelli 12, 27100, Pavia, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peroxisome proliferator-activated receptor gamma
A, B
304Homo 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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
QZQ
Query on QZQ

Download Ideal Coordinates CCD File 
C [auth A]Betulinic Acid
C30 H46 O3
UTRVNRSDMIXTLN-BMTJSWHCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
QZQ Binding MOAD:  5LSG Kd: 4000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.229 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.86α = 90
b = 60.85β = 102.48
c = 118.03γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-09
    Type: Initial release
  • Version 1.1: 2024-01-17
    Changes: Advisory, Data collection, Database references, Refinement description