3OOB

Structural and functional insights of directly targeting Pin1 by Epigallocatechin-3-gallate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.89 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1.

Urusova, D.V.Shim, J.H.Kim, D.J.Jung, S.K.Zykova, T.A.Carper, A.Bode, A.M.Dong, Z.

(2011) Cancer Prev Res (Phila) 4: 1366-1377

  • DOI: https://doi.org/10.1158/1940-6207.CAPR-11-0301
  • Primary Citation of Related Structures:  
    3OOB

  • PubMed Abstract: 

    The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate-induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.


  • Organizational Affiliation

    The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. zgdong@hi.umn.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1163Homo sapiensMutation(s): 1 
Gene Names: PIN1
EC: 5.2.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for Q13526 (Homo sapiens)
Explore Q13526 
Go to UniProtKB:  Q13526
PHAROS:  Q13526
GTEx:  ENSG00000127445 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13526
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
KDH Binding MOAD:  3OOB Kd: 2.16e+4 (nM) from 1 assay(s)
PDBBind:  3OOB Kd: 2.16e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.89 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.409α = 90
b = 69.409β = 90
c = 79.268γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-08-17
    Type: Initial release
  • Version 1.1: 2011-08-24
    Changes: Other
  • Version 1.2: 2011-11-30
    Changes: Database references
  • Version 1.3: 2017-11-08
    Changes: Refinement description
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations, Structure summary