2J8Z

Crystal Structure of human P53 inducible oxidoreductase (TP53I3,PIG3)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.228 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Three-Dimensional Structure and Enzymatic Function of Proapoptotic Human P53-Inducible Quinone Oxidoreductase Pig3.

Porte, S.Valencia, E.Yakovtseva, E.A.Borras, E.Shafqat, N.Debreczeny, J.E.Pike, A.C.W.Oppermann, U.Farres, J.Fita, I.Pares, X.

(2009) J Biol Chem 284: 17194

  • DOI: https://doi.org/10.1074/jbc.M109.001800
  • Primary Citation of Related Structures:  
    2J8Z

  • PubMed Abstract: 

    Tumor suppressor p53 regulates the expression of p53-induced genes (PIG) that trigger apoptosis. PIG3 or TP53I3 is the only known member of the medium chain dehydrogenase/reductase superfamily induced by p53 and is used as a proapoptotic marker. Although the participation of PIG3 in the apoptotic pathway is proven, the protein and its mechanism of action were never characterized. We analyzed human PIG3 enzymatic function and found NADPH-dependent reductase activity with ortho-quinones, which is consistent with the classification of PIG3 in the quinone oxidoreductase family. However, the activity is much lower than that of zeta-crystallin, a better known quinone oxidoreductase. In addition, we report the crystallographic structure of PIG3, which allowed the identification of substrate- and cofactor-binding sites, with residues fully conserved from bacteria to human. Tyr-59 in zeta-crystallin (Tyr-51 in PIG3) was suggested to participate in the catalysis of quinone reduction. However, kinetics of Tyr/Phe and Tyr/Ala mutants of both enzymes demonstrated that the active site Tyr is not catalytic but may participate in substrate binding, consistent with a mechanism based on propinquity effects. It has been proposed that PIG3 contribution to apoptosis would be through oxidative stress generation. We found that in vitro activity and in vivo overexpression of PIG3 accumulate reactive oxygen species. Accordingly, an inactive PIG3 mutant (S151V) did not produce reactive oxygen species in cells, indicating that enzymatically active protein is necessary for this function. This supports that PIG3 action is through oxidative stress produced by its enzymatic activity and provides essential knowledge for eventual control of apoptosis.


  • Organizational Affiliation

    From the Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
QUINONE OXIDOREDUCTASE354Homo sapiensMutation(s): 0 
EC: 1
UniProt & NIH Common Fund Data Resources
Find proteins for Q53FA7 (Homo sapiens)
Explore Q53FA7 
Go to UniProtKB:  Q53FA7
PHAROS:  Q53FA7
GTEx:  ENSG00000115129 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ53FA7
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
B [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.228 
  • Space Group: P 43 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.86α = 90
b = 46.86β = 90
c = 315.93γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2006-11-06
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description