2af2 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
SODC_HUMAN Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
SOD1 has to undergo several post-translational modifications before reaching its mature form. The protein requires insertion of zinc and copper atoms, followed by the formation of a conserved S-S bond between Cys-57 and Cys-146 (human numbering), which makes the protein fully active. In this report an NMR structural investigation of the reduced SH-SH form of thermostable E,Zn-as-SOD1 (E is empty; as is C6A, C111S) is reported, characterizing the protein just before the last step leading to the mature form. The structure is compared with that of the oxidized S-S form as well as with that of the yeast SOD1 complexed with its copper chaperone, CCS. Local conformational rearrangements upon disulfide bridge reduction are localized in the region near Cys-57 that is completely exposed to the solvent in the present structure, at variance with the oxidized forms. There is a local disorder around Cys-57 that may serve for protein-protein recognition and may possibly be involved in intermolecular S-S bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The structure allows us to further discuss the copper loading mechanism in SOD1.
Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form.,Banci L, Bertini I, Cantini F, D'Amelio N, Gaggelli E J Biol Chem. 2006 Jan 27;281(4):2333-7. Epub 2005 Nov 14. PMID:16291742[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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↑Yonashiro R, Sugiura A, Miyachi M, Fukuda T, Matsushita N, Inatome R, Ogata Y, Suzuki T, Dohmae N, Yanagi S. Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation. Mol Biol Cell. 2009 Nov;20(21):4524-30. doi: 10.1091/mbc.E09-02-0112. Epub 2009, Sep 9. PMID:19741096 doi:10.1091/mbc.E09-02-0112
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↑Elam JS, Taylor AB, Strange R, Antonyuk S, Doucette PA, Rodriguez JA, Hasnain SS, Hayward LJ, Valentine JS, Yeates TO, Hart PJ. Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS. Nat Struct Biol. 2003 Jun;10(6):461-7. PMID:12754496 doi:10.1038/nsb935
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↑Jones CT, Swingler RJ, Brock DJ. Identification of a novel SOD1 mutation in an apparently sporadic amyotrophic lateral sclerosis patient and the detection of Ile113Thr in three others. Hum Mol Genet. 1994 Apr;3(4):649-50. PMID:8069312
↑Esteban J, Rosen DR, Bowling AC, Sapp P, McKenna-Yasek D, O'Regan JP, Beal MF, Horvitz HR, Brown RH Jr. Identification of two novel mutations and a new polymorphism in the gene for Cu/Zn superoxide dismutase in patients with amyotrophic lateral sclerosis. Hum Mol Genet. 1994 Jun;3(6):997-8. PMID:7951252
↑Kostrzewa M, Burck-Lehmann U, Muller U. Autosomal dominant amyotrophic lateral sclerosis: a novel mutation in the Cu/Zn superoxide dismutase-1 gene. Hum Mol Genet. 1994 Dec;3(12):2261-2. PMID:7881433
↑Aoki M, Ogasawara M, Matsubara Y, Narisawa K, Nakamura S, Itoyama Y, Abe K. Familial amyotrophic lateral sclerosis (ALS) in Japan associated with H46R mutation in Cu/Zn superoxide dismutase gene: a possible new subtype of familial ALS. J Neurol Sci. 1994 Oct;126(1):77-83. PMID:7836951
↑Suthers G, Laing N, Wilton S, Dorosz S, Waddy H. "Sporadic" motoneuron disease due to familial SOD1 mutation with low penetrance. Lancet. 1994 Dec 24-31;344(8939-8940):1773. PMID:7997024
↑Jones CT, Shaw PJ, Chari G, Brock DJ. Identification of a novel exon 4 SOD1 mutation in a sporadic amyotrophic lateral sclerosis patient. Mol Cell Probes. 1994 Aug;8(4):329-30. PMID:7870076 doi:https://dx.doi.org/S0890-8508(84)71046-2
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↑Sjalander A, Beckman G, Deng HX, Iqbal Z, Tainer JA, Siddique T. The D90A mutation results in a polymorphism of Cu,Zn superoxide dismutase that is prevalent in northern Sweden and Finland. Hum Mol Genet. 1995 Jun;4(6):1105-8. PMID:7655469
↑Deng HX, Tainer JA, Mitsumoto H, Ohnishi A, He X, Hung WY, Zhao Y, Juneja T, Hentati A, Siddique T. Two novel SOD1 mutations in patients with familial amyotrophic lateral sclerosis. Hum Mol Genet. 1995 Jun;4(6):1113-6. PMID:7655471
↑Orrell R, de Belleroche J, Marklund S, Bowe F, Hallewell R. A novel SOD mutant and ALS. Nature. 1995 Apr 6;374(6522):504-5. PMID:7700376 doi:https://dx.doi.org/10.1038/374504a0
↑Andersen PM, Nilsson P, Ala-Hurula V, Keranen ML, Tarvainen I, Haltia T, Nilsson L, Binzer M, Forsgren L, Marklund SL. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat Genet. 1995 May;10(1):61-6. PMID:7647793 doi:https://dx.doi.org/10.1038/ng0595-61
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↑Hosler BA, Nicholson GA, Sapp PC, Chin W, Orrell RW, de Belleroche JS, Esteban J, Hayward LJ, Mckenna-Yasek D, Yeung L, Cherryson AK, Dench JE, Wilton SD, Laing NG, Horvitz HR, Brown RH Jr. Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis. Neuromuscul Disord. 1996 Oct;6(5):361-6. PMID:8938700
↑Morita M, Aoki M, Abe K, Hasegawa T, Sakuma R, Onodera Y, Ichikawa N, Nishizawa M, Itoyama Y. A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan. Neurosci Lett. 1996 Feb 23;205(2):79-82. PMID:8907321
↑Orrell RW, Marklund SL, deBelleroche JS. Familial ALS is associated with mutations in all exons of SOD1: a novel mutation in exon 3 (Gly72Ser). J Neurol Sci. 1997 Dec 9;153(1):46-9. PMID:9455977
↑Kikugawa K, Nakano R, Inuzuka T, Kokubo Y, Narita Y, Kuzuhara S, Yoshida S, Tsuji S. A missense mutation in the SOD1 gene in patients with amyotrophic lateral sclerosis from the Kii Peninsula and its vicinity, Japan. Neurogenetics. 1997 Sep;1(2):113-5. PMID:10732812
↑Bereznai B, Winkler A, Borasio GD, Gasser T. A novel SOD1 mutation in an Austrian family with amyotrophic lateral sclerosis. Neuromuscul Disord. 1997 Mar;7(2):113-6. PMID:9131652
↑Ratovitski T, Corson LB, Strain J, Wong P, Cleveland DW, Culotta VC, Borchelt DR. Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds. Hum Mol Genet. 1999 Aug;8(8):1451-60. PMID:10400992
↑Penco S, Schenone A, Bordo D, Bolognesi M, Abbruzzese M, Bugiani O, Ajmar F, Garre C. A SOD1 gene mutation in a patient with slowly progressing familial ALS. Neurology. 1999 Jul 22;53(2):404-6. PMID:10430435
↑Murakami T, Warita H, Hayashi T, Sato K, Manabe Y, Mizuno S, Yamane K, Abe K. A novel SOD1 gene mutation in familial ALS with low penetrance in females. J Neurol Sci. 2001 Aug 15;189(1-2):45-7. PMID:11535232
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↑Alexander MD, Traynor BJ, Miller N, Corr B, Frost E, McQuaid S, Brett FM, Green A, Hardiman O. "True" sporadic ALS associated with a novel SOD-1 mutation. Ann Neurol. 2002 Nov;52(5):680-3. PMID:12402272 doi:10.1002/ana.10369
↑Niwa J, Ishigaki S, Hishikawa N, Yamamoto M, Doyu M, Murata S, Tanaka K, Taniguchi N, Sobue G. Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity. J Biol Chem. 2002 Sep 27;277(39):36793-8. Epub 2002 Jul 26. PMID:12145308 doi:10.1074/jbc.M206559200
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↑Furukawa Y, Kaneko K, Yamanaka K, O'Halloran TV, Nukina N. Complete loss of post-translational modifications triggers fibrillar aggregation of SOD1 in the familial form of amyotrophic lateral sclerosis. J Biol Chem. 2008 Aug 29;283(35):24167-76. doi: 10.1074/jbc.M802083200. Epub 2008, Jun 13. PMID:18552350 doi:10.1074/jbc.M802083200
↑Banci L, Bertini I, Boca M, Girotto S, Martinelli M, Valentine JS, Vieru M. SOD1 and amyotrophic lateral sclerosis: mutations and oligomerization. PLoS One. 2008 Feb 27;3(2):e1677. doi: 10.1371/journal.pone.0001677. PMID:18301754 doi:10.1371/journal.pone.0001677
↑del Grande A, Luigetti M, Conte A, Mancuso I, Lattante S, Marangi G, Stipa G, Zollino M, Sabatelli M. A novel L67P SOD1 mutation in an Italian ALS patient. Amyotroph Lateral Scler. 2011 Mar;12(2):150-2. doi: 10.3109/17482968.2011.551939., Epub 2011 Jan 19. PMID:21247266 doi:10.3109/17482968.2011.551939
↑Chio A, Borghero G, Pugliatti M, Ticca A, Calvo A, Moglia C, Mutani R, Brunetti M, Ossola I, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Cossu P, Abramzon Y, Johnson JO, Nalls MA, Arepalli S, Chong S, Hernandez DG, Traynor BJ, Restagno G. Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Arch Neurol. 2011 May;68(5):594-8. doi: 10.1001/archneurol.2010.352. Epub 2011, Jan 10. PMID:21220647 doi:10.1001/archneurol.2010.352
↑Banci L, Bertini I, Cantini F, D'Amelio N, Gaggelli E. Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. J Biol Chem. 2006 Jan 27;281(4):2333-7. Epub 2005 Nov 14. PMID:16291742 doi:https://dx.doi.org/10.1074/jbc.M506497200
