2rk3: Difference between revisions
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'''Structure of A104T DJ-1''' | {{Structure | ||
|PDB= 2rk3 |SIZE=350|CAPTION= <scene name='initialview01'>2rk3</scene>, resolution 1.05Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= | |||
|GENE= PARK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Structure of A104T DJ-1''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2RK3 is a [ | 2RK3 is a [[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=2RK3 OCA]. | ||
==Reference== | ==Reference== | ||
Structural Impact of Three Parkinsonism-Associated Missense Mutations on Human DJ-1(,)., Lakshminarasimhan M, Maldonado MT, Zhou W, Fink AL, Wilson MA, Biochemistry. 2008 Feb 5;47(5):1381-92. Epub 2008 Jan 9. PMID:[http:// | Structural Impact of Three Parkinsonism-Associated Missense Mutations on Human DJ-1(,)., Lakshminarasimhan M, Maldonado MT, Zhou W, Fink AL, Wilson MA, Biochemistry. 2008 Feb 5;47(5):1381-92. Epub 2008 Jan 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18181649 18181649] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ubl conjugation]] | [[Category: ubl conjugation]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:36:54 2008'' | ||
Revision as of 16:36, 20 March 2008
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| 2rk3, resolution 1.05Å | |||||||||||||
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| Gene: | PARK7 (Homo sapiens) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Structure of A104T DJ-1
Overview
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.
About this Structure
2RK3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural Impact of Three Parkinsonism-Associated Missense Mutations on Human DJ-1(,)., Lakshminarasimhan M, Maldonado MT, Zhou W, Fink AL, Wilson MA, Biochemistry. 2008 Feb 5;47(5):1381-92. Epub 2008 Jan 9. PMID:18181649
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