PDBsum entry 1p5f

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Unknown function PDB id
Protein chain
186 a.a. *
Waters ×252
* Residue conservation analysis

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Title The 1.1-A resolution crystal structure of dj-1, The protein mutated in autosomal recessive early onset parkinson'S disease.
Authors M.A.Wilson, J.L.Collins, Y.Hod, D.Ringe, G.A.Petsko.
Ref. Proc Natl Acad Sci U S A, 2003, 100, 9256-9261. [DOI no: 10.1073/pnas.1133288100]
PubMed id 12855764
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.
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).
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