2c9u: Difference between revisions
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==Overview== | ==Overview== | ||
Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of, oxidative stress. Mutations in SOD1 are linked to the familial form of, amyotrophic lateral sclerosis. Several hypotheses for their toxicity, involve the mis-metallation of the enzyme. We present atomic-resolution, crystal structures and biophysical data for human SOD1 in three, metallation states: Zn-Zn, Cu-Zn and as-isolated. These data represent the, first atomic-resolution structures for human SOD1, the first structure of, a reduced SOD1, and the first structure of a fully Zn-substituted SOD1, enzyme. Recombinantly expressed as-isolated SOD1 contains a mixture of Zn, and Cu at the Cu-binding site. The Zn-Zn structure appears to be at least, as stable as the correctly (Cu-Zn) metallated enzyme. These data raise the, possibility that in a cellular environment with low availability of free, copper, Zn-Zn may be the preferred metallation state of SOD1 prior to its, interaction with the copper chaperone. | Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of, oxidative stress. Mutations in SOD1 are linked to the familial form of, amyotrophic lateral sclerosis. Several hypotheses for their toxicity, involve the mis-metallation of the enzyme. We present atomic-resolution, crystal structures and biophysical data for human SOD1 in three, metallation states: Zn-Zn, Cu-Zn and as-isolated. These data represent the, first atomic-resolution structures for human SOD1, the first structure of, a reduced SOD1, and the first structure of a fully Zn-substituted SOD1, enzyme. Recombinantly expressed as-isolated SOD1 contains a mixture of Zn, and Cu at the Cu-binding site. The Zn-Zn structure appears to be at least, as stable as the correctly (Cu-Zn) metallated enzyme. These data raise the, possibility that in a cellular environment with low availability of free, copper, Zn-Zn may be the preferred metallation state of SOD1 prior to its, interaction with the copper chaperone. | ||
==Disease== | |||
Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147450 147450]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: zn superoxide dismutase]] | [[Category: zn superoxide dismutase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:13:08 2007'' | ||
