Superoxide dismutase 1: identification of a novel mutation in a case of familial amyotrophic lateral sclerosis.
AuthorsKostrzewa M, Damian MS, Müller U
JournalHum Genet
PubMed ID8682505
'Mutation analysis of the superoxide dismutase gene SOD1 in a familial case of amyotrophic lateral sclerosis revealed a T --> C transition at codon 151 of exon 5. This mutation results in the substitution of an isoleucine for a threonine. It appears to affect formation of dimers of the protein ... More
Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis.
Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding ... More
Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase.
AuthorsStrange RW, Yong CW, Smith W, Hasnain SS
JournalProc Natl Acad Sci U S A
PubMed ID17548825
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 ... More
Structural characterization of zinc-deficient human superoxide dismutase and implications for ALS.
AuthorsRoberts BR, Tainer JA, Getzoff ED, Malencik DA, Anderson SR, Bomben VC, Meyers KR, Karplus PA, Beckman JS
JournalJ Mol Biol
PubMed ID17888947
Over 130 mutations to copper, zinc superoxide dismutase (SOD) are implicated in the selective death of motor neurons found in 25% of patients with familial amyotrophic lateral sclerosis (ALS). Despite their widespread distribution, ALS mutations appear positioned to cause structural and misfolding defects. Such defects decrease SOD's affinity for zinc, ... More