Oxyl and Hydroxyl Radical Transfer in Mitochondrial Amidoxime Reducing Component-Catalyzed Nitrite Reduction
Open accessAbstract
A combination of electron paramagnetic resonance (EPR) spectroscopy and computational approaches has provided insight into the nature of the reaction coordinate for the one-electron reduction of nitrite by the mitochondrial amidoxime reducing component (mARC) enzyme. The results show that a paramagnetic Mo(V) species is generated when reduced enzyme is exposed to nitrite, and an analysis of the resulting EPR hyperfine parameters confirms that mARC is remarkably similar to the low-pH form of sulfite oxidase. Two mechanisms for nitrite reduction have been considered. The first shows a modest reaction barrier of 14 kcal/mol for the formation of ·NO from unprotonated nitrite substrate. In marked contrast, protonation of the substrate oxygen proximal to Mo in the Mo(IV)-O-N-O substrate-bound species results in barrierless conversion to products. A fragment orbital analysis reveals a high degree of Mo-O(H)-N-O covalency that provides a π-orbital pathway for one-electron transfer to the substrate and defines orbital constraints on the Mo-substrate geometry for productive catalysis in mARC and other pyranopterin molybdenum enzymes that catalyze this one-electron transformation.
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- Authors
- Yang, J., Giles, L. J., Ruppelt, C., Mendel, R. R., Bittner, F., & Kirk, M. L.
- Affiliations
- University of New Mexico (US)
- Technische Universität Braunschweig (DE)
- Corresponding author
- Mendel, Ralf R.
- Bittner, Florian
- Kirk, Martin L.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-04-21
- Volume
- 137
- Issue
- 16
- Pages
- 5276-5279
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC4872596
- OpenAlex
- W2419522566
- Cited by
- 43
- References
- 24
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 3 · 2016: 5 · 2015: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM 057378)
- Deutsche Forschungsgemeinschaft (Bi 1075/2-2)
- Topics
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
- Keywords
- nitrite reduction, single electron transfer, molybdenum enzymes, sulfite oxidase, nitric oxide radical, reaction coordinate, reaction barriers, enzyme mechanism
- MeSH terms
- Electron Spin Resonance Spectroscopy, Electron Transport, Mitochondria, Models, Molecular, Molybdenum, Nitrites, Oxidation-Reduction, Oxidoreductases, Arabidopsis, Hydroxyl Radical, Arabidopsis Proteins, Sulfite Oxidase
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