Sandbox GGC1

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NMOs are FMN-dependent enzymes that can quickly and efficiently catalyze the oxidation of P3N. They can also oxidize alkyl nitronates but with lower catalytic efficiency in comparison to P3N.<ref> Francis K, Nishino SF, Spain JC, Gadda G. A novel activity for fungal nitronate monooxygenase: detoxification of the metabolic inhibitor propionate-3-nitronate. Arch Biochem Biophys. 2012;521(1–2):84–89.</ref><ref>Gadda G, Francis K. Nitronate monooxygenase, a model for anionic flavin semiquinone intermediates in oxidative catalysis. Arch Biochem Biophys. 2010;493(1):53–61.</ref> Recent structural studies suggest there are two classes of NMOs, Class I and Class II.<ref>Salvi F, Agniswamy J, Yuan H, et al. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II.J Biol Chem. 2014;289(34):23764–23775.</ref> Class I NMOs contain about 450 NMO gene products from bacteria, fungi, and animals. The enzymes in this class only oxidize P3N and nitronate analogues. Class II NMOs consists of small groups of ten fungal gene products and can oxidize nitronate and nitroalkaline analogues.<ref> Salvi F, Agniswamy J, Yuan H, et al. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II.J Biol Chem. 2014;289(34):23764–23775.</ref>
NMOs are FMN-dependent enzymes that can quickly and efficiently catalyze the oxidation of P3N. They can also oxidize alkyl nitronates but with lower catalytic efficiency in comparison to P3N.<ref> Francis K, Nishino SF, Spain JC, Gadda G. A novel activity for fungal nitronate monooxygenase: detoxification of the metabolic inhibitor propionate-3-nitronate. Arch Biochem Biophys. 2012;521(1–2):84–89.</ref><ref>Gadda G, Francis K. Nitronate monooxygenase, a model for anionic flavin semiquinone intermediates in oxidative catalysis. Arch Biochem Biophys. 2010;493(1):53–61.</ref> Recent structural studies suggest there are two classes of NMOs, Class I and Class II.<ref>Salvi F, Agniswamy J, Yuan H, et al. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II.J Biol Chem. 2014;289(34):23764–23775.</ref> Class I NMOs contain about 450 NMO gene products from bacteria, fungi, and animals. The enzymes in this class only oxidize P3N and nitronate analogues. Class II NMOs consists of small groups of ten fungal gene products and can oxidize nitronate and nitroalkaline analogues.<ref> Salvi F, Agniswamy J, Yuan H, et al. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II.J Biol Chem. 2014;289(34):23764–23775.</ref>
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In Class I NMOs, the enzyme mechanism is first initiated by a single electron transfer from P3N to the flavin that is enzyme-bound. The product is then oxidized by dioxygen and forms superoxide. The superoxide and P3N radial will then interact in the active site and form 3-peroxy-3-nitro-propanoate, which will decay to products with time.<ref>Smitherman C, Gadda G. Evidence for a transient peroxynitro acidin the reaction catalyzed by nitronate monooxygenase with propio-nate 3-nitronate. Biochemistry. 2013;52(15):2694–2704.</ref>
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In Class I NMOs, the enzyme mechanism is first initiated by a single electron transfer from P3N to the flavin that is enzyme-bound. The product is then oxidized by dioxygen and forms superoxide. The superoxide and P3N radial will then interact in the active site and form 3-peroxy-3-nitro-propanoate, which will decay to products with time.<ref>Smitherman C, Gadda G. Evidence for a transient peroxynitro acid in the reaction catalyzed by nitronate monooxygenase with propionate 3-nitronate. Biochemistry. 2013;52(15):2694–2704.</ref>
== Disease ==
== Disease ==
P3N can be considered a toxic compound that is commonly found in legumes, fungi, and leaf beetles. During hydrolysis, P3N is released from esters and acts as an irreversible inhibitor of mitochondrial succinate dehydrogenase. <ref>Hipkin CR, Simpson DJ, Wainwright SJ, Salem MA. Nitrification by plants that also fix nitrogen. Nature. 2004;430(6995):98–101</ref> Succinate dehydrogenase is a key enzyme in the Kreb's cycle and the electron transport chain for oxidative phosphorylation. Because this is inhibited, it can lead to a variety of neurological disorders and can even cause death. <ref>Francis K, Smitherman C, Nishino SF, Spain JC, Gadda G. The biochemistry of the metabolic poison propionate 3-nitronate and its conjugate acid, 3-nitropropionate. IUBMB Life. 2013;65(9):759–768.</ref>
P3N can be considered a toxic compound that is commonly found in legumes, fungi, and leaf beetles. During hydrolysis, P3N is released from esters and acts as an irreversible inhibitor of mitochondrial succinate dehydrogenase. <ref>Hipkin CR, Simpson DJ, Wainwright SJ, Salem MA. Nitrification by plants that also fix nitrogen. Nature. 2004;430(6995):98–101</ref> Succinate dehydrogenase is a key enzyme in the Kreb's cycle and the electron transport chain for oxidative phosphorylation. Because this is inhibited, it can lead to a variety of neurological disorders and can even cause death. <ref>Francis K, Smitherman C, Nishino SF, Spain JC, Gadda G. The biochemistry of the metabolic poison propionate 3-nitronate and its conjugate acid, 3-nitropropionate. IUBMB Life. 2013;65(9):759–768.</ref>
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P3N is found in plant shoots and leaves which more than likely acts as a defense mechanism for herbivores. In laboratories, P3N is also used in small amounts to poison mitochondria in rats and other animals that induce symptoms similar to Huntington's disease. This is used to develop possible treatments.
== Structural highlights ==
== Structural highlights ==

Revision as of 19:37, 22 April 2018

Crystal Structure of yeast nitronate monooxygenase from Cyberlindera saturnas

Caption for this structure

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References

  1. ↑ Huerta C, Borek D, Machius M, Grishin NV, Zhang H. Structure and Mechanism of a Eukaryotic FMN Adenylyltransferase. Journal of molecular biology. 2009;389(2):388-400. doi:10.1016/j.jmb.2009.04.022.
  2. ↑ Francis K, Nishino SF, Spain JC, Gadda G. A novel activity for fungal nitronate monooxygenase: detoxification of the metabolic inhibitor propionate-3-nitronate. Arch Biochem Biophys. 2012;521(1–2):84–89.
  3. ↑ Gadda G, Francis K. Nitronate monooxygenase, a model for anionic flavin semiquinone intermediates in oxidative catalysis. Arch Biochem Biophys. 2010;493(1):53–61.
  4. ↑ Salvi F, Agniswamy J, Yuan H, et al. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II.J Biol Chem. 2014;289(34):23764–23775.
  5. ↑ Salvi F, Agniswamy J, Yuan H, et al. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II.J Biol Chem. 2014;289(34):23764–23775.
  6. ↑ Smitherman C, Gadda G. Evidence for a transient peroxynitro acid in the reaction catalyzed by nitronate monooxygenase with propionate 3-nitronate. Biochemistry. 2013;52(15):2694–2704.
  7. ↑ Hipkin CR, Simpson DJ, Wainwright SJ, Salem MA. Nitrification by plants that also fix nitrogen. Nature. 2004;430(6995):98–101
  8. ↑ Francis K, Smitherman C, Nishino SF, Spain JC, Gadda G. The biochemistry of the metabolic poison propionate 3-nitronate and its conjugate acid, 3-nitropropionate. IUBMB Life. 2013;65(9):759–768.
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