| Structural highlights
Disease
SODC_HUMAN Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:105400. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.[1] [2] [3] [4] [5] [6] [7] [8] [:][9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45]
Function
SODC_HUMAN Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Publication Abstract from PubMed
Cu/Zn superoxide dismutase-1 (SOD1) mutations are causative for a subset of amyotrophic lateral sclerosis (ALS) cases. These mutations lead to structural instability, aggregation and ultimately motor neuron death. We have determined crystal structures of SOD1 in complex with a naphthalene-catechol-linked compound which binds with low micro-molar affinity to a site important for oxidative damage-induced aggregation. SOD1 Trp32 oxidation is indeed significantly inhibited by ligand binding. Our work shows how compound linking can be applied successfully to ligand interactions on the SOD1 surface to generate relatively good binding strength. The ligand, positioned in a region important for SOD1 fibrillation, offers the possibility that it, or a similar compound, could prevent the abnormal self-association that drives SOD1 toxicity in ALS.
Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation.,Manjula R, Wright GSA, Strange RW, Padmanabhan B FEBS Lett. 2018 May;592(10):1725-1737. doi: 10.1002/1873-3468.13055. Epub 2018, May 11. PMID:29679384[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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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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- ↑ 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
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- ↑ Yulug IG, Katsanis N, de Belleroche J, Collinge J, Fisher EM. An improved protocol for the analysis of SOD1 gene mutations, and a new mutation in exon 4. Hum Mol Genet. 1995 Jun;4(6):1101-4. PMID:7655468
- ↑ 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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- ↑ Sapp PC, Rosen DR, Hosler BA, Esteban J, McKenna-Yasek D, O'Regan JP, Horvitz HR, Brown RH Jr. Identification of three novel mutations in the gene for Cu/Zn superoxide dismutase in patients with familial amyotrophic lateral sclerosis. Neuromuscul Disord. 1995 Sep;5(5):353-7. PMID:7496169
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- ↑ 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
- ↑ Watanabe M, Aoki M, Abe K, Shoji M, Iizuka T, Ikeda Y, Hirai S, Kurokawa K, Kato T, Sasaki H, Itoyama Y. A novel missense point mutation (S134N) of the Cu/Zn superoxide dismutase gene in a patient with familial motor neuron disease. Hum Mutat. 1997;9(1):69-71. PMID:8990014 doi:<69::AID-HUMU14>3.0.CO;2-N 10.1002/(SICI)1098-1004(1997)9:1<69::AID-HUMU14>3.0.CO;2-N
- ↑ Kawamata J, Shimohama S, Takano S, Harada K, Ueda K, Kimura J. Novel G16S (GGC-AGC) mutation in the SOD-1 gene in a patient with apparently sporadic young-onset amyotrophic lateral sclerosis. Hum Mutat. 1997;9(4):356-8. PMID:9101297 doi:<356::AID-HUMU9>3.0.CO;2-3 10.1002/(SICI)1098-1004(1997)9:4<356::AID-HUMU9>3.0.CO;2-3
- ↑ 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
- ↑ Gellera C, Castellotti B, Riggio MC, Silani V, Morandi L, Testa D, Casali C, Taroni F, Di Donato S, Zeviani M, Mariotti C. Superoxide dismutase gene mutations in Italian patients with familial and sporadic amyotrophic lateral sclerosis: identification of three novel missense mutations. Neuromuscul Disord. 2001 May;11(4):404-10. PMID:11369193
- ↑ 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
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- ↑ Andersen PM, Sims KB, Xin WW, Kiely R, O'Neill G, Ravits J, Pioro E, Harati Y, Brower RD, Levine JS, Heinicke HU, Seltzer W, Boss M, Brown RH Jr. Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph Lateral Scler Other Motor Neuron Disord. 2003 Jun;4(2):62-73. PMID:14506936
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- ↑ 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
- ↑ Manjula R, Wright GSA, Strange RW, Padmanabhan B. Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation. FEBS Lett. 2018 May;592(10):1725-1737. PMID:29679384 doi:10.1002/1873-3468.13055
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