2c9v
From Proteopedia
| Line 6: | Line 6: | ||
==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== | ||
| Line 37: | Line 40: | ||
[[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 21:13:11 2007'' |
Revision as of 19:06, 12 November 2007
|
ATOMIC RESOLUTION STRUCTURE OF CU-ZN HUMAN SUPEROXIDE DISMUTASE
Contents |
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.
Disease
Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]
About this Structure
2C9V is a Single protein structure of sequence from Homo sapiens with CU, ZN, SO4 and NA as ligands. Active as Superoxide dismutase, with EC number 1.15.1.1 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Variable metallation of human superoxide dismutase: atomic resolution crystal structures of Cu-Zn, Zn-Zn and as-isolated wild-type enzymes., Strange RW, Antonyuk SV, Hough MA, Doucette PA, Valentine JS, Hasnain SS, J Mol Biol. 2006 Mar 10;356(5):1152-62. Epub 2005 Dec 12. PMID:16406071
Page seeded by OCA on Mon Nov 12 21:13:11 2007
Categories: Homo sapiens | Single protein | Superoxide dismutase | Antonyuk, S. | Doucette, P.A. | Hasnain, S.S. | Hough, M.A. | Strange, R.W. | Valentine, J.S. | CU | NA | SO4 | ZN | Acetylation | Amyotrophic lateral sclerosis | Antioxidant | Copper | Disease mutation | Human cu | Metal-binding | Oxidoreductase | Oxioreductase | Zinc | Zn superoxide dismutase
