PDBsum entry 1p5f

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protein links
Unknown function PDB id
Protein chain
186 a.a. *
Waters ×252
* Residue conservation analysis
PDB id:
Name: Unknown function
Title: Crystal structure of human dj-1
Structure: RNA-binding protein regulatory subunit. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.10Å     R-factor:   0.139     R-free:   0.161
Authors: M.A.Wilson,J.L.Collins,Y.Hod,D.Ringe,G.A.Petsko
Key ref:
M.A.Wilson et al. (2003). The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease. Proc Natl Acad Sci U S A, 100, 9256-9261. PubMed id: 12855764 DOI: 10.1073/pnas.1133288100
26-Apr-03     Release date:   12-Aug-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q99497  (PARK7_HUMAN) -  Protein DJ-1
189 a.a.
186 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  


DOI no: 10.1073/pnas.1133288100 Proc Natl Acad Sci U S A 100:9256-9261 (2003)
PubMed id: 12855764  
The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease.
M.A.Wilson, J.L.Collins, Y.Hod, D.Ringe, G.A.Petsko.
Mutations in DJ-1, a human gene with homologues in organisms from all kingdoms of life, have been shown to be associated with autosomal recessive, early onset Parkinson's disease (PARK7). We report here the three-dimensional structure of the DJ-1 protein, determined at a resolution of 1.1 A by x-ray crystallography. The chain fold of DJ-1 resembles those of a bacterial protein, PfpI, that has been annotated as a cysteine protease, and of a domain of a bacterial catalase whose role in the activity of that enzyme is uncertain. In contrast to PfpI, a hexameric protein whose oligomeric structure is essential for its putative proteolytic activity, DJ-1 is a dimer with completely different intersubunit contacts. The proposed catalytic triad of PfpI is absent from the corresponding region of the structure of DJ-1, and biochemical assays fail to detect any protease activity for purified DJ-1. A highly conserved cysteine residue, which is catalytically essential in homologues of DJ-1, shows an extreme sensitivity to radiation damage and may be subject to other forms of oxidative modification as well. The structure suggests that the loss of function caused by the Parkinson's-associated mutation L166P in DJ-1 is due to destabilization of the dimer interface. Taken together, the crystal structure of human DJ-1 plus other observations suggest the possible involvement of this protein in the cellular oxidative stress response and a general etiology of neurodegenerative diseases.
  Selected figure(s)  
Figure 1.
Fig. 1. (a and b) Two views of the DJ-1 crystallographic dimer. Monomer A is purple and monomer B is green. The view in b is rotated by 90° with respect to the view in a. In both views, Cys-106 is yellow and Leu-166, which is mutated to proline in PARK7 familial PD, is red. In b, the unusual coaxial arrangement of the two C-terminal -helices (G and H) at the dimer interface is highlighted. The figure was made with POVSCRIPT+ (50).
Figure 4.
Fig. 4. Residues near the nucleophile elbow region of DJ-1 do not comprise a catalytic triad. (a) A ribbon diagram of the DJ-1 monomer is shown, with residues Glu-18, Cys-106, and His-126 in yellow. Leu-166, which is mutated to proline in PARK7 familial PD, is red. (b) A closer view of the nucleophile elbow region with 2F[o] - F[c] electron density contoured at 1.0 . Although the identity of the residues is correct for a catalytic triad, their conformation prohibits proton shuttling by the canonical mechanism of a serine/cysteine protease or a glutamine amidotransferase. The figure was made with POVSCRIPT+ (50).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21322020 F.Ghazavi, Z.Fazlali, S.S.Banihosseini, S.R.Hosseini, M.H.Kazemi, S.Shojaee, K.Parsa, H.Sadeghi, F.Sina, M.Rohani, G.A.Shahidi, N.Ghaemi, M.Ronaghi, and E.Elahi (2011).
PRKN, DJ-1, and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ-1 mutations.
  Mov Disord, 26, 80-89.  
20806408 C.P.Ramsey, and B.I.Giasson (2010).
L10p and P158DEL DJ-1 mutations cause protein instability, aggregation, and dimerization impairments.
  J Neurosci Res, 88, 3111-3124.  
20089532 C.P.Ramsey, E.Tsika, H.Ischiropoulos, and B.I.Giasson (2010).
DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human alpha-syn toxicity.
  Hum Mol Genet, 19, 1425-1437.  
20124404 F.Kthiri, H.T.Le, V.Gautier, T.Caldas, A.Malki, A.Landoulsi, C.Bohn, P.Bouloc, and G.Richarme (2010).
Protein aggregation in a mutant deficient in yajL, the bacterial homolog of the Parkinsonism-associated protein DJ-1.
  J Biol Chem, 285, 10328-10336.  
20304780 J.Chen, L.Li, and L.S.Chin (2010).
Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage.
  Hum Mol Genet, 19, 2395-2408.  
21258649 L.J.Martin (2010).
Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases.
  Pharmaceuticals (Basel), 3, 839-915.  
20187230 M.R.Cookson (2010).
DJ-1, PINK1, and their effects on mitochondrial pathways.
  Mov Disord, 25, S44-S48.  
20156966 S.Deeg, M.Gralle, K.Sroka, M.Bähr, F.S.Wouters, and P.Kermer (2010).
BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity.
  J Cell Biol, 188, 505-513.  
20014057 T.Inoue, M.Kitagawa, T.Tanaka, S.Nakagawa, and T.Koyama (2010).
Depression and major depressive disorder in patients with Parkinson's disease.
  Mov Disord, 25, 44-49.  
18711745 E.Junn, W.H.Jang, X.Zhao, B.S.Jeong, and M.M.Mouradian (2009).
Mitochondrial localization of DJ-1 leads to enhanced neuroprotection.
  J Neurosci Res, 87, 123-129.  
19497122 H.Nural, P.He, T.Beach, L.Sue, W.Xia, and Y.Shen (2009).
Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients.
  Mol Neurodegener, 4, 23.  
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.  
20087465 K.Yamane, Y.Kitamura, T.Yanagida, K.Takata, D.Yanagisawa, T.Taniguchi, T.Taira, and H.Ariga (2009).
Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson's Disease-Linked PARK7.
  Int J Mol Sci, 10, 4789-4804.  
19521672 M.R.Landon, R.L.Lieberman, Q.Q.Hoang, S.Ju, J.M.Caaveiro, S.D.Orwig, D.Kozakov, R.Brenke, G.Y.Chuang, D.Beglov, S.Vajda, G.A.Petsko, and D.Ringe (2009).
Detection of ligand binding hot spots on protein surfaces via fragment-based methods: application to DJ-1 and glucocerebrosidase.
  J Comput Aided Mol Des, 23, 491-500.  
19074999 N.M.Karabacak, L.Li, A.Tiwari, L.J.Hayward, P.Hong, M.L.Easterling, and J.N.Agar (2009).
Sensitive and specific identification of wild type and variant proteins from 8 to 669 kDa using top-down mass spectrometry.
  Mol Cell Proteomics, 8, 846-856.  
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.  
  20046643 T.Yanagida, J.Tsushima, Y.Kitamura, D.Yanagisawa, K.Takata, T.Shibaike, A.Yamamoto, T.Taniguchi, H.Yasui, T.Taira, S.Morikawa, T.Inubushi, I.Tooyama, and H.Ariga (2009).
Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.
  Oxid Med Cell Longev, 2, 36-42.  
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
18646040 B.Bindukumar, S.Schwartz, R.Aalinkeel, S.Mahajan, A.Lieberman, and K.Chadha (2008).
Proteomic profiling of the effect of prostate-specific antigen on prostate cancer cells.
  Prostate, 68, 1531-1545.  
18162323 C.Maita, S.Tsuji, I.Yabe, S.Hamada, A.Ogata, H.Maita, S.M.Iguchi-Ariga, H.Sasaki, and H.Ariga (2008).
Secretion of DJ-1 into the serum of patients with Parkinson's disease.
  Neurosci Lett, 431, 86-89.  
18822273 C.P.Ramsey, and B.I.Giasson (2008).
The E163K DJ-1 mutant shows specific antioxidant deficiency.
  Brain Res, 1239, 1.  
17882163 D.Yanagisawa, Y.Kitamura, M.Inden, K.Takata, T.Taniguchi, S.Morikawa, M.Morita, T.Inubushi, I.Tooyama, T.Taira, S.M.Iguchi-Ariga, A.Akaike, and H.Ariga (2008).
DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats.
  J Cereb Blood Flow Metab, 28, 563-578.  
18313759 F.J.Lee, and F.Liu (2008).
Genetic factors involved in the pathogenesis of Parkinson's disease.
  Brain Res Rev, 58, 354-364.  
18436956 G.Malgieri, and D.Eliezer (2008).
Structural effects of Parkinson's disease linked DJ-1 mutations.
  Protein Sci, 17, 855-868.  
18309325 J.S.Mo, M.Y.Kim, E.J.Ann, J.A.Hong, and H.S.Park (2008).
DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death.
  Cell Death Differ, 15, 1030-1041.  
18181649 M.Lakshminarasimhan, M.T.Maldonado, W.Zhou, A.L.Fink, and M.A.Wilson (2008).
Structural impact of three Parkinsonism-associated missense mutations on human DJ-1.
  Biochemistry, 47, 1381-1392.
PDB codes: 2rk3 2rk4 2rk6 3b36 3b38 3b3a
18626009 M.P.van der Brug, J.Blackinton, J.Chandran, L.Y.Hao, A.Lal, K.Mazan-Mamczarz, J.Martindale, C.Xie, R.Ahmad, K.J.Thomas, A.Beilina, J.R.Gibbs, J.Ding, A.J.Myers, M.Zhan, H.Cai, N.M.Bonini, M.Gorospe, and M.R.Cookson (2008).
RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways.
  Proc Natl Acad Sci U S A, 105, 10244-10249.  
18689799 N.Zhong, and J.Xu (2008).
Synergistic activation of the human MnSOD promoter by DJ-1 and PGC-1alpha: regulation by SUMOylation and oxidation.
  Hum Mol Genet, 17, 3357-3367.  
18707128 P.C.Anderson, and V.Daggett (2008).
Molecular basis for the structural instability of human DJ-1 induced by the L166P mutation associated with Parkinson's disease.
  Biochemistry, 47, 9380-9393.  
18514968 S.Balaji, L.M.Iyer, M.M.Babu, and L.Aravind (2008).
Comparison of transcription regulatory interactions inferred from high-throughput methods: what do they reveal?
  Trends Genet, 24, 319-323.  
18922803 S.S.Cha, H.I.Jung, H.Jeon, Y.J.An, I.K.Kim, S.Yun, H.J.Ahn, K.C.Chung, S.H.Lee, P.G.Suh, and S.O.Kang (2008).
Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner.
  J Biol Chem, 283, 34069-34075.
PDB code: 3bwe
17766438 E.Andres-Mateos, C.Perier, L.Zhang, B.Blanchard-Fillion, T.M.Greco, B.Thomas, H.S.Ko, M.Sasaki, H.Ischiropoulos, S.Przedborski, T.M.Dawson, and V.L.Dawson (2007).
DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase.
  Proc Natl Acad Sci U S A, 104, 14807-14812.  
17299411 J.C.Paterna, A.Leng, E.Weber, J.Feldon, and H.Büeler (2007).
DJ-1 and Parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice.
  Mol Ther, 15, 698-704.  
  17593875 L.J.Martin (2007).
Transgenic mice with human mutant genes causing Parkinson's disease and amyotrophic lateral sclerosis provide common insight into mechanisms of motor neuron selective vulnerability to degeneration.
  Rev Neurosci, 18, 115-136.  
16390825 A.Sekito, S.Koide-Yoshida, T.Niki, T.Taira, S.M.Iguchi-Ariga, and H.Ariga (2006).
DJ-1 interacts with HIPK1 and affects H2O2-induced cell death.
  Free Radic Res, 40, 155-165.  
16894167 M.C.Meulener, K.Xu, L.Thomson, L.Thompson, H.Ischiropoulos, and N.M.Bonini (2006).
Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.
  Proc Natl Acad Sci U S A, 103, 12517-12522.  
16495942 P.M.Abou-Sleiman, M.M.Muqit, and N.W.Wood (2006).
Expanding insights of mitochondrial dysfunction in Parkinson's disease.
  Nat Rev Neurosci, 7, 207-219.  
16615060 S.Kubo, N.Hattori, and Y.Mizuno (2006).
Recessive Parkinson's disease.
  Mov Disord, 21, 885-893.  
15976810 Y.Shinbo, T.Niki, T.Taira, H.Ooe, K.Takahashi-Niki, C.Maita, C.Seino, S.M.Iguchi-Ariga, and H.Ariga (2006).
Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities.
  Cell Death Differ, 13, 96.  
16022590 D.J.Moore, A.B.West, V.L.Dawson, and T.M.Dawson (2005).
Molecular pathophysiology of Parkinson's disease.
  Annu Rev Neurosci, 28, 57-87.  
15983381 E.Junn, H.Taniguchi, B.S.Jeong, X.Zhao, H.Ichijo, and M.M.Mouradian (2005).
Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.
  Proc Natl Acad Sci U S A, 102, 9691-9696.  
16298734 H.M.Li, T.Niki, T.Taira, S.M.Iguchi-Ariga, and H.Ariga (2005).
Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress.
  Free Radic Res, 39, 1091-1099.  
15935068 M.C.Meulener, C.L.Graves, D.M.Sampathu, C.E.Armstrong-Gold, N.M.Bonini, and B.I.Giasson (2005).
DJ-1 is present in a large molecular complex in human brain tissue and interacts with alpha-synuclein.
  J Neurochem, 93, 1524-1532.  
15952880 M.R.Cookson (2005).
The biochemistry of Parkinson's disease.
  Annu Rev Biochem, 74, 29-52.  
15721235 M.S.Goldberg, A.Pisani, M.Haburcak, T.A.Vortherms, T.Kitada, C.Costa, Y.Tong, G.Martella, A.Tscherter, A.Martins, G.Bernardi, B.L.Roth, E.N.Pothos, P.Calabresi, and J.Shen (2005).
Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1.
  Neuron, 45, 489-496.  
15766664 R.H.Kim, M.Peters, Y.Jang, W.Shi, M.Pintilie, G.C.Fletcher, C.DeLuca, J.Liepa, L.Zhou, B.Snow, R.C.Binari, A.S.Manoukian, M.R.Bray, F.F.Liu, M.S.Tsao, and T.W.Mak (2005).
DJ-1, a novel regulator of the tumor suppressor PTEN.
  Cancer Cell, 7, 263-273.  
20396458 W.Lin, and U.J.Kang (2005).
Neuroprotective therapy in Parkinson's disease: current status and new directions from experimental and genetic clues.
  J Clin Neurol, 1, 107-120.  
15272266 E.Bossy-Wetzel, R.Schwarzenbacher, and S.A.Lipton (2004).
Molecular pathways to neurodegeneration.
  Nat Med, 10, S2-S9.  
15187181 J.V.Gray, G.A.Petsko, G.C.Johnston, D.Ringe, R.A.Singer, and M.Werner-Washburne (2004).
"Sleeping beauty": quiescence in Saccharomyces cerevisiae.
  Microbiol Mol Biol Rev, 68, 187-206.  
15056757 M.A.Hough, J.G.Grossmann, S.V.Antonyuk, R.W.Strange, P.A.Doucette, J.A.Rodriguez, L.J.Whitson, P.J.Hart, L.J.Hayward, J.S.Valentine, and S.S.Hasnain (2004).
Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutants.
  Proc Natl Acad Sci U S A, 101, 5976-5981.
PDB codes: 1uxl 1uxm
14745011 M.A.Wilson, C.V.St Amour, J.L.Collins, D.Ringe, and G.A.Petsko (2004).
The 1.8-A resolution crystal structure of YDR533Cp from Saccharomyces cerevisiae: a member of the DJ-1/ThiJ/PfpI superfamily.
  Proc Natl Acad Sci U S A, 101, 1531-1536.
PDB code: 1rw7
15130476 M.Graille, S.Quevillon-Cheruel, N.Leulliot, C.Z.Zhou, I.Li de la Sierra Gallay, L.Jacquamet, J.L.Ferrer, D.Liger, A.Poupon, J.Janin, and H.van Tilbeurgh (2004).
Crystal structure of the YDR533c S. cerevisiae protein, a class II member of the Hsp31 family.
  Structure, 12, 839-847.
PDB codes: 1qvv 1qvw 1qvz
15522970 M.J.Lindberg, J.Normark, A.Holmgren, and M.Oliveberg (2004).
Folding of human superoxide dismutase: disulfide reduction prevents dimerization and produces marginally stable monomers.
  Proc Natl Acad Sci U S A, 101, 15893-15898.  
15173574 M.S.Sastry, P.M.Quigley, W.G.Hol, and F.Baneyx (2004).
The linker-loop region of Escherichia coli chaperone Hsp31 functions as a gate that modulates high-affinity substrate binding at elevated temperatures.
  Proc Natl Acad Sci U S A, 101, 8587-8592.  
15236834 O.von Bohlen und Halbach, A.Schober, and K.Krieglstein (2004).
Genes, proteins, and neurotoxins involved in Parkinson's disease.
  Prog Neurobiol, 73, 151-177.  
15503154 P.M.Abou-Sleiman, D.G.Healy, and N.W.Wood (2004).
Causes of Parkinson's disease: genetics of DJ-1.
  Cell Tissue Res, 318, 185-188.  
14691241 P.M.Quigley, K.Korotkov, F.Baneyx, and W.G.Hol (2004).
A new native EcHsp31 structure suggests a key role of structural flexibility for chaperone function.
  Protein Sci, 13, 269-277.
PDB code: 1pv2
15181200 R.M.Canet-Avilés, M.A.Wilson, D.W.Miller, R.Ahmad, C.McLendon, S.Bandyopadhyay, M.J.Baptista, D.Ringe, G.A.Petsko, and M.R.Cookson (2004).
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.
  Proc Natl Acad Sci U S A, 101, 9103-9108.
PDB code: 1soa
15070401 S.Bandyopadhyay, and M.R.Cookson (2004).
Evolutionary and functional relationships within the DJ1 superfamily.
  BMC Evol Biol, 4, 6.  
15502874 S.Shendelman, A.Jonason, C.Martinat, T.Leete, and A.Abeliovich (2004).
DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation.
  PLoS Biol, 2, e362.  
14749723 T.Taira, Y.Saito, T.Niki, S.M.Iguchi-Ariga, K.Takahashi, and H.Ariga (2004).
DJ-1 has a role in antioxidative stress to prevent cell death.
  EMBO Rep, 5, 213-218.  
15538967 V.Rachakonda, T.H.Pan, and W.D.LE (2004).
Biomarkers of neurodegenerative disorders: how good are they?
  Cell Res, 14, 347-358.  
15060002 X.S.Puente, and C.López-Otín (2004).
A genomic analysis of rat proteases and protease inhibitors.
  Genome Res, 14, 609-622.  
12886009 M.R.Cookson (2003).
Crystallizing ideas about Parkinson's disease.
  Proc Natl Acad Sci U S A, 100, 9111-9113.  
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.