Cited by 43Metal-Catalyzed Oxygenation MechanismsRedox biology and oxidative stressMetalloenzymes and iron-sulfur proteins

Comparison of two yeast MnSODs: Mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans

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Sheng, Yuewei, Stich, Troy A., Barnese, Kevin, Gralla, Edith B., Cascio, Duilio, Britt, R. David, Cabelli, Diane E., Valentine, Joan Selverstone·2011·Journal of the American Chemical Society

Abstract

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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  1. [31]Campbell KA Dissertation Thesis 1999 University of California-Davis
  2. [51]Miller AF Vance CK Biochemistry 2001 40 13079 11669646
  3. [56]Melendez JA Dasgupta J Subbaram S Connor KM Rodriguez AM Tirosh O Beckman JS JourD’Heuil D Antioxid Redox Sign 2006 8 1295 16910777

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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
Published
2011-11-30
Volume
133
Issue
51
Pages
20878-20889
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
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
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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