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PDBsum entry 2or3

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protein ligands Protein-protein interface(s) links
Chaperone PDB id
2or3
Jmol
Contents
Protein chain
187 a.a. *
Ligands
SO4 ×2
Waters ×583
* Residue conservation analysis
PDB id:
2or3
Name: Chaperone
Title: Pre-oxidation complex of human dj-1
Structure: Protein dj-1. Chain: a, b. Synonym: oncogene dj1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: park7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.20Å     R-factor:   0.136     R-free:   0.182
Authors: A.C.Witt,M.Lakshminarasimhan,M.A.Wilson
Key ref: A.C.Witt et al. (2008). Cysteine pKa depression by a protonated glutamic acid in human DJ-1. Biochemistry, 47, 7430-7440. PubMed id: 18570440
Date:
01-Feb-07     Release date:   13-Feb-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q99497  (PARK7_HUMAN) -  Protein DJ-1
Seq:
Struc:
189 a.a.
187 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   11 terms 
  Biological process     response to stress   65 terms 
  Biochemical function     protein binding     31 terms  

 

 
Biochemistry 47:7430-7440 (2008)
PubMed id: 18570440  
 
 
Cysteine pKa depression by a protonated glutamic acid in human DJ-1.
A.C.Witt, M.Lakshminarasimhan, B.C.Remington, S.Hasim, E.Pozharski, M.A.Wilson.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19124468 J.Blackinton, M.Lakshminarasimhan, K.J.Thomas, R.Ahmad, E.Greggio, A.S.Raza, M.R.Cookson, and M.A.Wilson (2009).
Formation of a Stabilized Cysteine Sulfinic Acid Is Critical for the Mitochondrial Function of the Parkinsonism Protein DJ-1.
  J Biol Chem, 284, 6476-6485.
PDB codes: 3ezg 3f71
19293155 J.Waak, S.S.Weber, K.Görner, C.Schall, H.Ichijo, T.Stehle, and P.J.Kahle (2009).
Oxidizable Residues Mediating Protein Stability and Cytoprotective Interaction of DJ-1 with Apoptosis Signal-regulating Kinase 1.
  J Biol Chem, 284, 14245-14257.  
19670233 P.Acín, J.Rayó, A.Guerrero, and C.Quero (2009).
Improved resolution in the acidic and basic region of 2-DE of insect antennae proteins using hydroxyethyl disulfide.
  Electrophoresis, 30, 2613-2616.  
19686841 P.J.Kahle, J.Waak, and T.Gasser (2009).
DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders.
  Free Radic Biol Med, 47, 1354-1361.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.