2v0a
From Proteopedia
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| - | [[Image:2v0a.gif|left|200px]] | + | [[Image:2v0a.gif|left|200px]] |
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| - | '''ATOMIC RESOLUTION CRYSTAL STRUCTURE OF HUMAN SUPEROXIDE DISMUTASE''' | + | {{Structure |
| + | |PDB= 2v0a |SIZE=350|CAPTION= <scene name='initialview01'>2v0a</scene>, resolution 1.15Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+F'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=ACT:ACETATE ION'>ACT</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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''ATOMIC RESOLUTION CRYSTAL STRUCTURE OF HUMAN SUPEROXIDE DISMUTASE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2V0A is a [ | + | 2V0A 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=2V0A OCA]. |
==Reference== | ==Reference== | ||
| - | Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase., Strange RW, Yong CW, Smith W, Hasnain SS, Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10040-4. Epub 2007 Jun 4. PMID:[http:// | + | Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase., Strange RW, Yong CW, Smith W, Hasnain SS, Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10040-4. Epub 2007 Jun 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17548825 17548825] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: human cu]] | [[Category: human cu]] | ||
[[Category: metal-binding]] | [[Category: metal-binding]] | ||
| - | [[Category: molecular | + | [[Category: molecular dinamic]] |
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
[[Category: oxioreductase]] | [[Category: oxioreductase]] | ||
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[[Category: zn superoxide dismutase]] | [[Category: zn superoxide dismutase]] | ||
| - | ''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 18:41:52 2008'' |
Revision as of 16:41, 20 March 2008
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| , resolution 1.15Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , and | ||||||
| Activity: | Superoxide dismutase, with EC number 1.15.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ATOMIC RESOLUTION CRYSTAL STRUCTURE OF HUMAN SUPEROXIDE DISMUTASE
Contents |
Overview
Mutations of the gene encoding Cu-Zn superoxide dismutase (SOD1) cause 20% of the familial cases of the progressive neurodegenerative disease ALS. A growing body of evidence suggests that in familial ALS (FALS) it is the molecular behavior of the metal-depleted SOD1 dimer that leads to a gain of toxic properties by misfolding, unfolding, and aggregation. Structural studies have so far provided static snapshots on the behavior of the wild-type enzyme and some of the FALS mutants. New approaches are required to map out the structural trajectories of the molecule. Here, using our 1.15-A resolution structure of fully metallated human SOD1 and highly parallelized molecular dynamics code on a high-performance capability computer, we have undertaken molecular dynamics calculations to 4,000 ps to reveal the first stages of misfolding caused by metal deletion. Large spatial and temporal fluctuations of the "electrostatic" and "Zn-binding" loops adjacent to the metal-binding sites are observed in the apo-enzyme relative to the fully metallated dimer. These early misfolding events expose the beta-barrels of the dimer to the external environment, allowing close interactions with adjacent molecules. Protection of the beta-edge of the protein can be partially restored by incorporating a single Zn molecule per dimer. These calculations reveal an essential step in the formation of the experimentally observed self-aggregations of metal-depleted FALS mutant SOD1. This result also has implications for the role of demetallated wild-type SOD1 in sporadic cases of ALS, for which the molecular cause still remains undiscovered.
Disease
Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]
About this Structure
2V0A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase., Strange RW, Yong CW, Smith W, Hasnain SS, Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10040-4. Epub 2007 Jun 4. PMID:17548825
Page seeded by OCA on Thu Mar 20 18:41:52 2008
Categories: Homo sapiens | Single protein | Superoxide dismutase | Antonyuk, S. | Hasnain, S S. | Smith, W. | Strange, R W. | Yong, C W. | ACT | CU | SO4 | ZN | Acetylation | Amyotrophic lateral sclerosis | Antioxidant | Copper | Disease mutation | Human cu | Metal-binding | Molecular dinamic | Oxidoreductase | Oxioreductase | Zinc | Zn superoxide dismutase
