Cited by 80Metal-Catalyzed Oxygenation MechanismsEnzyme Structure and FunctionProtein Structure and Dynamics

Structure of fully reduced bovine copper zinc superoxide dismutase at 1.15 Å

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Hough, Michael A, Hasnain, S.Samar·2003·Structure

Abstract

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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Crossref · 10.1016/s0969-2126(03)00155-2

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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.”

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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
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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