2VGE

Crystal structure of the C-terminal region of human iASPP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Biochemical and Structural Studies of Aspp Proteins Reveal Differential Binding to P53, P63 and P73

Robinson, R.A.Lu, X.Jones, E.Y.Siebold, C.

(2008) Structure 16: 259

  • DOI: https://doi.org/10.1016/j.str.2007.11.012
  • Primary Citation of Related Structures:  
    2VGE

  • PubMed Abstract: 

    ASPP1 and ASPP2 are activators of p53-dependent apoptosis, whereas iASPP is an inhibitor of p53. Binding assays showed differential binding for C-terminal domains of iASPP and ASPP2 to the core domains of p53 family members p53, p63, and p73. We also determined a high-resolution crystal structure for the C terminus of iASPP, comprised of four ankyrin repeats and an SH3 domain. The crystal lattice revealed an interaction between eight sequential residues in one iASPP molecule and the p53-binding site of a neighboring molecule. ITC confirmed that a peptide corresponding to the crystallographic interaction shows specific binding to iASPP. The contributions of ankyrin repeat residues, in addition to those of the SH3 domain, generate distinctive architecture at the p53-binding site suitable for inhibition by small molecules. These results suggest that the binding properties of iASPP render it a target for antitumor therapeutics and provide a peptide-based template for compound design.


  • Organizational Affiliation

    Cancer Research UK Receptor Structure Research Group, Division of Structural Biology, Henry Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RELA-ASSOCIATED INHIBITOR229Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q8WUF5 (Homo sapiens)
Explore Q8WUF5 
Go to UniProtKB:  Q8WUF5
PHAROS:  Q8WUF5
GTEx:  ENSG00000104881 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8WUF5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.969α = 90
b = 67.545β = 90
c = 50.49γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-02-05
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description