Copper–zinc superoxide dismutase: Why not pH-dependent?
Abstract
Copper−zinc superoxide dismutase (CuZnSOD) catalyzes the disproportionation of superoxide to hydrogen peroxide and dioxygen at diffusion controlled rates. Previous mechanistic studies have focused on the dramatic electrostatic guidance mechanism by which superoxide is drawn into the active site of this enzyme. Another striking but less understood feature of this enzyme is its ability to dismutate superoxide over a wide range of pH (5−9.5) without any change in rate-determining step or structural changes at the active site copper. To investigate the explanation for this pH independence, we have redetermined the rate of superoxide disproportionation, k cat, catalyzed by the zinc-deficient form (Cu-apoSOD) of the enzyme as a function of pH and have found that it is pH-dependent, in contrast to the native enzyme, even under conditions in which the copper ion does not leave the native copper-binding site. In addition, we have determined the rate of reduction, k 1, of Cu-apoSOD by superoxide and have found that this step of the catalytic cycle is pH-independent. We conclude that the reoxidation rate, k 2, of the catalytic cycle is pH-dependent for Cu-apoSOD. These results have led us to propose that the key role of the zinc and of the histidyl imidazolate that bridges copper and zinc in CuZnSOD is to aid in the rapid dissociation of the product peroxide.
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A detailed examination of the first reaction using a pulse radiolysis technique showed that the enzymatic reduction and oxidation of superoxide were independent of pH. However, the second reaction was pH-dependent.
“A detailed examination of the first reaction using a pulse radiolysis technique showed that the enzymatic reduction and oxidation of superoxide were independent of pH. However, the second reaction was pH-dependent [78].”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [78]
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Self-citation
- Authors
- Ellerby, L. M., Cabelli, D. E., Graden, J. A., & Valentine, J. S.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 1996-01-01
- Volume
- 118
- Issue
- 28
- Pages
- 6556-6561
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2067888080
- Cited by
- 184
- References
- 30
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 9 · 2019: 6 · 2018: 9 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 9
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institutes of Health
- Brookhaven National Laboratory
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
- Keywords
- copper-zinc superoxide dismutase, superoxide disproportionation, pH dependence, enzyme mechanism
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