Comparison of two yeast MnSODs: Mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans
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Human MnSOD is significantly more product-inhibited than bacterial MnSODs at high concentrations of superoxide (O(2)(-)). This behavior limits the amount of H(2)O(2) produced at high [O(2)(-)]; its desirability can be explained by the multiple roles of H(2)O(2) in mammalian cells, particularly its role in signaling. To investigate the mechanism of product inhibition in MnSOD, two yeast MnSODs, one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), were isolated and characterized. ScMnSOD and CaMnSODc are similar in catalytic kinetics, spectroscopy, and redox chemistry, and they both rest predominantly in the reduced state (unlike most other MnSODs). At high [O(2)(-)], the dismutation efficiencies of the yeast MnSODs surpass those of human and bacterial MnSODs, due to very low level of product inhibition. Optical and parallel-mode electron paramagnetic resonance (EPR) spectra suggest the presence of two Mn(3+) species in yeast Mn(3+)SODs, including the well-characterized 5-coordinate Mn(3+) species and a 6-coordinate L-Mn(3+) species with hydroxide as the putative sixth ligand (L). The first and second coordination spheres of ScMnSOD are more similar to bacterial than to human MnSOD. Gln154, an H-bond donor to the Mn-coordinated solvent molecule, is slightly further away from Mn in yeast MnSODs, which may result in their unusual resting state. Mechanistically, the high efficiency of yeast MnSODs could be ascribed to putative translocation of an outer-sphere solvent molecule, which could destabilize the inhibited complex and enhance proton transfer from protein to peroxide. Our studies on yeast MnSODs indicate the unique nature of human MnSOD in that it predominantly undergoes the inhibited pathway at high [O(2)(-)].
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The mechanism of Mn-SOD dismutation is complex.
“The mechanism of Mn-SOD dismutation is complex [83].”
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- Authors
- Sheng, Y., Stich, T. A., Barnese, K., Gralla, E. B., Cascio, D., Britt, R. D., Cabelli, D. E., & Valentine, J. S.
- Affiliations
- University of California, Los Angeles (US)
- University of California, Davis (US)
- Ewha Womans University (KR)
- Brookhaven National Laboratory (US)
- Corresponding author
- Cabelli, Diane E.
- Valentine, Joan Selverstone
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-11-30
- Volume
- 133
- Issue
- 51
- Pages
- 20878-20889
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC3268005
- OpenAlex
- W2071533285
- Cited by
- 43
- References
- 65
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Energy
- National Institute of General Medical Sciences (GM 48242, R29GM048242, R01GM048242)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK046828)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- manganese superoxide dismutase, product inhibition, superoxide dismutase, Saccharomyces cerevisiae, Candida albicans, hydrogen peroxide production, coordination sphere, resting state, proton transfer, redox chemistry, electron spin resonance
- MeSH terms
- Candida albicans, Electron Spin Resonance Spectroscopy, Kinetics, Models, Molecular, Oxidation-Reduction, Saccharomyces cerevisiae, Superoxide Dismutase, Crystallography, X-Ray, Catalytic Domain, Protein Multimerization
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