ArticleBiochemistry2009
Structural and biophysical properties of the pathogenic SOD1 variant H46R/H48Q.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Decoupling metabolic defense: Mutational and recombinational chaos in Sod1-deficient cells.PLoS genetics · 2026Article
- Clinical characterization and founder effect analysis in Chinese amyotrophic lateral sclerosis patients withAnnals of medicine · 2024Article
- Extreme diversity of 12 cations in folding ALS-linked hSOD1 unveils novel hSOD1-dependent mechanisms for FeScientific reports · 2023Article
- Structure of a superoxide dismutase from a tardigrade: Ramazzottius varieornatus strain YOKOZUNA-1.Acta crystallographica. Section F, Structural biology communications · 2023Article
- Bridging the Bridging Imidazolate in the Bimetallic Center of the Cu/Zn SOD1 and ALS.Frontiers in chemistry · 2021Article
- Article
- Nucleation and kinetics of SOD1 aggregation in human cells for ALS1.Molecular and cellular biochemistry · 2020Article
- Mutations in Superoxide Dismutase 1 (Sod1) Linked to Familial Amyotrophic Lateral Sclerosis Can Disrupt High-Affinity Zinc-Binding Promoted by the Copper Chaperone for Sod1 (Ccs).Molecules (Basel, Switzerland) · 2020Article
- Copper-zinc superoxide dismutase (Sod1) activation terminates interaction between its copper chaperone (Ccs) and the cytosolic metal-binding domain of the copper importer Ctr1.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension.Acta neuropathologica · 2019Article
- A new function of copper zinc superoxide dismutase: as a regulatory DNA-binding protein in gene expression in response to intracellular hydrogen peroxide.Nucleic acids research · 2019Article
- The yeast copper chaperone for copper-zinc superoxide dismutase (CCS1) is a multifunctional chaperone promoting all levels of SOD1 maturation.The Journal of biological chemistry · 2019Article
- Structural Properties and Interaction Partners of Familial ALS-Associated SOD1 Mutants.Frontiers in neurology · 2019Review
- The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation.Nature communications · 2018Article
- Quantifying the Interaction between Copper-Zinc Superoxide Dismutase (Sod1) and its Copper Chaperone (Ccs1).Journal of proteomics & bioinformatics · 2018Article
- A molecular chaperone activity of CCS restores the maturation of SOD1 fALS mutants.Scientific reports · 2017Article
- The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase.Molecules (Basel, Switzerland) · 2017Review
- Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site.The Journal of biological chemistry · 2017Article
- S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.Scientific reports · 2017Article
- A faulty interaction between SOD1 and hCCS in neurodegenerative disease.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Over 100 mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Two pathogenic SOD1 mutations, His46Arg (H46R) and His48Gln (H48Q), affect residues that act as copper ligands in the wild type enzyme. Transgenic mice expressing a human SOD1 variant containing both mutations develop paralytic disease akin to ALS. Here we show that H46R/H48Q SOD1 possesses multiple characteristics that distinguish it from the wild type. These properties include the following: (1) an ablated copper-binding site, (2) a substantially weakened affinity for zinc, (3) a binding site for a calcium ion, (4) the ability to form stable heterocomplexes with the copper chaperone for SOD1 (CCS), and (5) compromised CCS-mediated oxidation of the intrasubunit disulfide bond in vivo. The results presented here, together with data on pathogenic SOD1 proteins coming from cell culture and transgenic mice, suggest that incomplete posttranslational modification of nascent SOD1 polypeptides via CCS may be a characteristic shared by familial ALS SOD1 mutants, leading to a population of destabilized, off-pathway folding intermediates that are toxic to motor neurons.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.