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PDBsum entry 3b3a

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protein ligands metals links
Chaperone PDB id
3b3a
Jmol
Contents
Protein chain
187 a.a. *
Ligands
EDO ×3
Metals
_CL
Waters ×208
* Residue conservation analysis
PDB id:
3b3a
Name: Chaperone
Title: Structure of e163k/r145e 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.
Resolution:
1.50Å     R-factor:   0.183     R-free:   0.203
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
Date:
19-Oct-07     Release date:   15-Jan-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q99497  (PARK7_HUMAN) -  Protein DJ-1
Seq:
Struc:
189 a.a.
187 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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 47:1381-1392 (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.
 
  ABSTRACT  
 
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.