3CY6

Crystal Structure of E18Q DJ-1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.168 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.155 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Cysteine pKa depression by a protonated glutamic acid in human DJ-1.

Witt, A.C.Lakshminarasimhan, M.Remington, B.C.Hasim, S.Pozharski, E.Wilson, M.A.

(2008) Biochemistry 47: 7430-7440

  • DOI: https://doi.org/10.1021/bi800282d
  • Primary Citation of Related Structures:  
    2OR3, 3CY6, 3CYF, 3CZ9, 3CZA

  • PubMed Abstract: 

    Human DJ-1, a disease-associated protein that protects cells from oxidative stress, contains an oxidation-sensitive cysteine (C106) that is essential for its cytoprotective activity. The origin of C106 reactivity is obscure, due in part to the absence of an experimentally determined p K a value for this residue. We have used atomic-resolution X-ray crystallography and UV spectroscopy to show that C106 has a depressed p K a of 5.4 +/- 0.1 and that the C106 thiolate accepts a hydrogen bond from a protonated glutamic acid side chain (E18). X-ray crystal structures and cysteine p K a analysis of several site-directed substitutions at residue 18 demonstrate that the protonated carboxylic acid side chain of E18 is required for the maximal stabilization of the C106 thiolate. A nearby arginine residue (R48) participates in a guanidinium stacking interaction with R28 from the other monomer in the DJ-1 dimer and elevates the p K a of C106 by binding an anion that electrostatically suppresses thiol ionization. Our results show that the ionizable residues (E18, R48, and R28) surrounding C106 affect its p K a in a way that is contrary to expectations based on the typical ionization behavior of glutamic acid and arginine. Lastly, a search of the Protein Data Bank (PDB) produces several candidate hydrogen-bonded aspartic/glutamic acid-cysteine interactions, which we propose are particularly common in the DJ-1 superfamily.


  • Organizational Affiliation

    Department of Biochemistry and Redox Biology Center, The University of Nebraska, Lincoln, Nebraska 68588-0664, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein DJ-1197Homo sapiensMutation(s): 1 
Gene Names: PARK7
UniProt & NIH Common Fund Data Resources
Find proteins for Q99497 (Homo sapiens)
Explore Q99497 
Go to UniProtKB:  Q99497
PHAROS:  Q99497
GTEx:  ENSG00000116288 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99497
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.168 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.155 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.78α = 90
b = 74.78β = 90
c = 75.443γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references
  • Version 1.3: 2023-08-30
    Changes: Data collection, Refinement description