PDBsum entry 2rk3

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protein links
Chaperone PDB id
Protein chain
187 a.a. *
Waters ×229
* Residue conservation analysis
PDB id:
Name: Chaperone
Title: Structure of a104t dj-1
Structure: Protein dj-1. Chain: a. Synonym: oncogene dj1, parkinson disease protein 7. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: park7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.05Å     R-factor:   0.133     R-free:   0.150
Authors: M.Lakshminarasimhan,M.T.Maldonado,W.Zhou,A.L.Fink,M.A.Wilson
Key ref: M.Lakshminarasimhan et al. (2008). Structural impact of three Parkinsonism-associated missense mutations on human DJ-1. Biochemistry, 47, 1381-1392. PubMed id: 18181649
16-Oct-07     Release date:   15-Jan-08    
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Protein chain
Pfam   ArchSchema ?
Q99497  (PARK7_HUMAN) -  Protein DJ-1
189 a.a.
187 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell body   16 terms 
  Biological process     mitochondrion organization   80 terms 
  Biochemical function     protein binding     33 terms  


Biochemistry 47:1381-1392 (2008)
PubMed id: 18181649  
Structural impact of three Parkinsonism-associated missense mutations on human DJ-1.
M.Lakshminarasimhan, M.T.Maldonado, W.Zhou, A.L.Fink, M.A.Wilson.
A number of missense mutations in the oxidative stress response protein DJ-1 are implicated in rare forms of familial Parkinsonism. The best-characterized Parkinsonian DJ-1 missense mutation, L166P, disrupts homodimerization and results in a poorly folded protein. The molecular basis by which the other Parkinsonism-associated mutations disrupt the function of DJ-1, however, is incompletely understood. In this study we show that three different Parkinsonism-associated DJ-1 missense mutations (A104T, E163K, and M26I) reduce the thermal stability of DJ-1 in solution by subtly perturbing the structure of DJ-1 without causing major folding defects or loss of dimerization. Atomic resolution X-ray crystallography shows that the A104T substitution introduces water and a discretely disordered residue into the core of the protein, E163K disrupts a key salt bridge with R145, and M26I causes packing defects in the core of the dimer. The deleterious effect of each Parkinsonism-associated mutation on DJ-1 is dissected by analysis of engineered substitutions (M26L, A104V, and E163K/R145E) that partially alleviate each of the defects introduced by the A104T, E163K and M26I mutations. In total, our results suggest that the protective function of DJ-1 can be compromised by diverse perturbations in its structural integrity, particularly near the junctions of secondary structural elements.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
19023331 S.Zucchelli, S.Vilotti, R.Calligaris, Z.S.Lavina, M.Biagioli, R.Foti, L.De Maso, M.Pinto, M.Gorza, E.Speretta, C.Casseler, G.Tell, G.Del Sal, and S.Gustincich (2009).
Aggresome-forming TTRAP mediates pro-apoptotic properties of Parkinson's disease-associated DJ-1 missense mutations.
  Cell Death Differ, 16, 428-438.  
18570440 A.C.Witt, M.Lakshminarasimhan, B.C.Remington, S.Hasim, E.Pozharski, and M.A.Wilson (2008).
Cysteine pKa depression by a protonated glutamic acid in human DJ-1.
  Biochemistry, 47, 7430-7440.
PDB codes: 2or3 3cy6 3cyf 3cz9 3cza
18822273 C.P.Ramsey, and B.I.Giasson (2008).
The E163K DJ-1 mutant shows specific antioxidant deficiency.
  Brain Res, 1239, 1.  
18436956 G.Malgieri, and D.Eliezer (2008).
Structural effects of Parkinson's disease linked DJ-1 mutations.
  Protein Sci, 17, 855-868.  
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.