ArticleJournal of molecular biology2014
Cu,Zn-superoxide dismutase without Zn is folded but catalytically inactive.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2025Review
- Optimum concentrations of potassium and zinc for better performance, nutritional, and biochemical quality of hydroponically cultivated Spinacia oleracea Cv. Virofly.Scientific reports · 2025Article
- Oxidative Stress in Healthy and Pathological Red Blood Cells.Biomolecules · 2023Review
- Evidence and Metabolic Implications for a New Non-Canonical Role of Cu-Zn Superoxide Dismutase.International journal of molecular sciences · 2023Article
- Mechanism of the Early Catalytic Events in the Collagenolysis by Matrix Metalloproteinase-1.Chemphyschem : a European journal of chemical physics and physical chemistry · 2023Article
- Review
- Development ofIranian journal of biotechnology · 2022Article
- Evaluation of ZnMolecules (Basel, Switzerland) · 2022Article
- Molecular and Biochemical Analysis of Duplicated Cytosolic CuZn Superoxide Dismutases of Rice andFrontiers in plant science · 2022Article
- Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules.The Journal of biological chemistry · 2021Review
- Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase.Heliyon · 2021Article
- Utilizing Ion Mobility-Mass Spectrometry to Investigate the Unfolding Pathway of Cu/Zn Superoxide Dismutase.Frontiers in chemistry · 2021Article
- Toxic and Physiological Metal Uptake and Release by Human Serum Transferrin.Biophysical journal · 2020Article
- Nucleation and kinetics of SOD1 aggregation in human cells for ALS1.Molecular and cellular biochemistry · 2020Article
- The Case for Enzymatic Competitive Metal Affinity Methods.ACS catalysis · 2020Article
- An Allosteric Pathway in Copper, Zinc Superoxide Dismutase Unravels the Molecular Mechanism of the G93A Amyotrophic Lateral Sclerosis-Linked Mutation.The journal of physical chemistry letters · 2019Article
- Investigation of Anti-SOD1 Antibodies Yields New Structural Insight into SOD1 Misfolding and Surprising Behavior of the Antibodies Themselves.ACS chemical biology · 2018Article
- Identification of novel superoxide dismutase isoenzymes in the olive (Olea europaea L.) pollen.BMC plant biology · 2018Article
- Prophylactic Zinc and Therapeutic Selenium Administration Increases the Antioxidant Enzyme Activity in the Rat Temporoparietal Cortex and Improves Memory after a Transient Hypoxia-Ischemia.Oxidative medicine and cellular longevity · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis has been linked to the gain of aberrant function of superoxide dismutase, Cu,Zn-SOD1 upon protein misfolding. The mechanism of SOD1 misfolding is thought to involve mutations leading to the loss of Zn, followed by protein unfolding and aggregation. We show that the removal of Zn from SOD1 may not lead to an immediate unfolding but immediately deactivates the enzyme through a combination of subtle structural and electronic effects. Using quantum mechanics/discrete molecular dynamics, we showed that both Zn-less wild-type (WT)-SOD1 and its D124N mutant that does not bind Zn have at least metastable folded states. In those states, the reduction potential of Cu increases, leading to the presence of detectable amounts of Cu(I) instead of Cu(II) in the active site, as confirmed experimentally. The Cu(I) protein cannot participate in the catalytic Cu(I)-Cu(II) cycle. However, even without the full reduction to Cu(I), the Cu site in the Zn-less variants of SOD1 is shown to be catalytically incompetent: unable to bind superoxide in a way comparable to the WT-SOD1. The changes are more radical and different in the D124N Zn-less mutant than in the Zn-less WT-SOD1, suggesting D124N being perhaps not the most adequate model for Zn-less SOD1. Overall, Zn in SOD1 appears to be influencing the Cu site directly by adjusting its reduction potential and geometry. Thus, the role of Zn in SOD1 is not just structural, as was previously thought; it is a vital part of the catalytic machinery.
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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.