1p5f: Difference between revisions
New page: left|200px<br /> <applet load="1p5f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p5f, resolution 1.10Å" /> '''Crystal Structure o... |
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[[Image:1p5f.gif|left|200px]]<br /> | [[Image:1p5f.gif|left|200px]]<br /><applet load="1p5f" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1p5f, resolution 1.10Å" /> | caption="1p5f, resolution 1.10Å" /> | ||
'''Crystal Structure of Human DJ-1'''<br /> | '''Crystal Structure of Human DJ-1'''<br /> | ||
==Overview== | ==Overview== | ||
Mutations in DJ-1, a human gene with homologues in organisms from all | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1P5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1P5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P5F OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Collins, J | [[Category: Collins, J L.]] | ||
[[Category: Hod, Y.]] | [[Category: Hod, Y.]] | ||
[[Category: Petsko, G | [[Category: Petsko, G A.]] | ||
[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
[[Category: Wilson, M | [[Category: Wilson, M A.]] | ||
[[Category: unknown function]] | [[Category: unknown function]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:25:16 2008'' | ||
Revision as of 15:25, 21 February 2008
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Crystal Structure of Human DJ-1
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Amyotrophic lateral sclerosis-Parkinsonism/dementia complex 2 OMIM:[602533], Parkinson disease 7, autosomal recessive early-onset OMIM:[602533]
About this StructureAbout this Structure
1P5F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease., Wilson MA, Collins JL, Hod Y, Ringe D, Petsko GA, Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9256-61. Epub 2003 Jul 10. PMID:12855764
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