1uxm: Difference between revisions
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|PDB= 1uxm |SIZE=350|CAPTION= <scene name='initialview01'>1uxm</scene>, resolution 1.90Å | |PDB= 1uxm |SIZE=350|CAPTION= <scene name='initialview01'>1uxm</scene>, resolution 1.90Å | ||
|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+L'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+L'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene> | |LIGAND= <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uxm OCA], [http://www.ebi.ac.uk/pdbsum/1uxm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uxm RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body of evidence suggests that a subset of mutations located close to the dimeric interface can lead to a major destabilization of the mutant enzymes. We have determined the crystal structures of the Ala4Val (A4V) and Ile113Thr (I113T) mutants to 1.9 and 1.6 A, respectively. In the A4V structure, small changes at the dimer interface result in a substantial reorientation of the two monomers. This effect is also seen in the case of the I113T crystal structure, but to a smaller extent. X-ray solution scattering data show that in the solution state, both of the mutants undergo a more pronounced conformational change compared with wild-type superoxide dismutase (SOD) than that observed in the A4V crystal structure. Shape reconstructions from the x-ray scattering data illustrate the nature of this destabilization. Comparison of these scattering data with those for bovine CuZn SOD measured at different temperatures shows that an analogous change in the scattering profile occurs for the bovine enzyme in the temperature range of 70-80 degrees C. These results demonstrate that the A4V and I113T mutants are substantially destabilized in comparison with wild-type SOD1, and it is possible that the pathogenic properties of this subset of familial amyotrophic lateral sclerosis mutants are at least in part due to this destabilization. | More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body of evidence suggests that a subset of mutations located close to the dimeric interface can lead to a major destabilization of the mutant enzymes. We have determined the crystal structures of the Ala4Val (A4V) and Ile113Thr (I113T) mutants to 1.9 and 1.6 A, respectively. In the A4V structure, small changes at the dimer interface result in a substantial reorientation of the two monomers. This effect is also seen in the case of the I113T crystal structure, but to a smaller extent. X-ray solution scattering data show that in the solution state, both of the mutants undergo a more pronounced conformational change compared with wild-type superoxide dismutase (SOD) than that observed in the A4V crystal structure. Shape reconstructions from the x-ray scattering data illustrate the nature of this destabilization. Comparison of these scattering data with those for bovine CuZn SOD measured at different temperatures shows that an analogous change in the scattering profile occurs for the bovine enzyme in the temperature range of 70-80 degrees C. These results demonstrate that the A4V and I113T mutants are substantially destabilized in comparison with wild-type SOD1, and it is possible that the pathogenic properties of this subset of familial amyotrophic lateral sclerosis mutants are at least in part due to this destabilization. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Valentine, J S.]] | [[Category: Valentine, J S.]] | ||
[[Category: Whitson, L J.]] | [[Category: Whitson, L J.]] | ||
[[Category: acetylation]] | [[Category: acetylation]] | ||
[[Category: amyotrophic lateral sclerosis]] | [[Category: amyotrophic lateral sclerosis]] | ||
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[[Category: zn superoxide dismutase]] | [[Category: zn superoxide dismutase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:16:46 2008'' | ||
Revision as of 00:16, 31 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Superoxide dismutase, with EC number 1.15.1.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
A4V MUTANT OF HUMAN SOD1
OverviewOverview
More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body of evidence suggests that a subset of mutations located close to the dimeric interface can lead to a major destabilization of the mutant enzymes. We have determined the crystal structures of the Ala4Val (A4V) and Ile113Thr (I113T) mutants to 1.9 and 1.6 A, respectively. In the A4V structure, small changes at the dimer interface result in a substantial reorientation of the two monomers. This effect is also seen in the case of the I113T crystal structure, but to a smaller extent. X-ray solution scattering data show that in the solution state, both of the mutants undergo a more pronounced conformational change compared with wild-type superoxide dismutase (SOD) than that observed in the A4V crystal structure. Shape reconstructions from the x-ray scattering data illustrate the nature of this destabilization. Comparison of these scattering data with those for bovine CuZn SOD measured at different temperatures shows that an analogous change in the scattering profile occurs for the bovine enzyme in the temperature range of 70-80 degrees C. These results demonstrate that the A4V and I113T mutants are substantially destabilized in comparison with wild-type SOD1, and it is possible that the pathogenic properties of this subset of familial amyotrophic lateral sclerosis mutants are at least in part due to this destabilization.
About this StructureAbout this Structure
1UXM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutants., Hough MA, Grossmann JG, Antonyuk SV, Strange RW, Doucette PA, Rodriguez JA, Whitson LJ, Hart PJ, Hayward LJ, Valentine JS, Hasnain SS, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5976-81. Epub 2004 Mar 31. PMID:15056757
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Superoxide dismutase
- Antonyuk, S V.
- Doucette, P A.
- Grossmann, J G.
- Hart, P J.
- Hasnain, S S.
- Hayward, L J.
- Hough, M A.
- Rodriguez, J A.
- Strange, R W.
- Valentine, J S.
- Whitson, L J.
- Acetylation
- Amyotrophic lateral sclerosis
- Antioxidant
- Copper
- Disease mutation
- Human cu
- Metal-binding
- Oxidoreductase
- Zinc
- Zn superoxide dismutase