Structure of fully reduced bovine copper zinc superoxide dismutase at 1.15 Å
Open accessAbstract
Copper zinc superoxide dismutase (CuZnSOD) forms a crucial component of the cellular response to oxidative stress by catalyzing the dismutation of the superoxide radical to hydrogen peroxide and water. Mutations in human CuZnSOD are associated with the development of familial amyotrophic lateral sclerosis (motor neuron disease). We have determined the structure of fully reduced bovine CuZnSOD to 1.15 A, the only atomic resolution structure for an intact CuZnSOD and one of only a small number for metalloproteins. For the first time, both subunits have been captured with the three coordinate Cu(I) ligation required by the generally accepted catalytic mechanism, where dismutation of the superoxide radical occurs via reduction of Cu. Furthermore, the improved resolution compared to previous studies (to 1.65 A) has allowed a more detailed examination of the metal center environment and its associated water network in the active site channel, facilitating the analysis of potential proton transfer routes.
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Copper is the redox active metal and zinc appears to play a role in the overall stability of the enzyme and in facilitating a high-pH-independence of enzyme activity.
“Copper is the redox active metal and zinc appears to play a role in the overall stability of the enzyme and in facilitating a high-pH-independence of enzyme activity [79], Figure 33.”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [79]
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- Authors
- Hough, M. A., & Hasnain, S. S.
- Affiliations
- Daresbury Laboratory (GB)
- Corresponding author
- Hasnain, S.Samar
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 11
- Issue
- 8
- Pages
- 937-946
- ISSN
- 0969-2126 (ISSN-L)
- OpenAlex
- W2085150103
- Cited by
- 80
- References
- 24
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 7 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- copper-zinc superoxide dismutase, metalloprotein structure, superoxide dismutation, catalytic mechanism, proton transfer, amyotrophic lateral sclerosis, oxidative stress
- MeSH terms
- Animals, Binding Sites, Cattle, Copper, Disulfides, Histidine, Ligands, Models, Molecular, Nitrogen, Oxidation-Reduction, Structure-Activity Relationship, Superoxide Dismutase, Water, Zinc, Crystallography, X-Ray, Dimerization
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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