Sandbox GGC1

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Crystal Structure of yeast nitronate monooxygenase from ''Cyberlindera saturnas''
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==Kinesin Motor Domain==
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<StructureSection load='6BKA' size='340' side='right' caption='Caption for this structure' scene=''>
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<StructureSection load='1bg2' size='340' side='right' caption='Kinesin Protein' scene=''>
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Kinesin is an ATP-dependent motor protein responsible for the transportation of cargo. It is a heterotetramer composed of light and heavy chains.
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Nitronate Monooxygenase (NMO) is an FMN-dependent (flavin mononucleotide) enzyme that oxidizes the neurotoxin propionate 3-nitronate (P3N). FMN is produced from riboflavin or Vitamin B2 by riboflavin kinase and can function as a prosthetic group for NADH dehydrogenase <ref>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.</ref>. NMO is widely known as the best system for P3N detoxification in many different organisms.
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== '''Function''' ==
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* Moving cargo usually from the center of the cell to the margins <br/>
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* Involved in cell replication and axonal signaling
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== '''Disease''' ==
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*Charcot Marie Tooth (CMT): Charcot Marie Tooth is one of many diseases that affect the peripheral nervous system. Individuals may suffer physical disabilities due to weakness in transmission of signals firing from the central nervous system
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== Function ==
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== '''Structural highlights''' ==
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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>
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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>
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;Scene #1: Kinesin structure is composed of eight anti-parallel Beta sheets and three alpha helices on opposite sides <scene name='75/752263/Alpha_beta_sheets/5'> Alpha-beta structure </scene>
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== Disease ==
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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. This induces symptoms similar to Huntington's disease and is used to develop possible treatments.<ref>Guyot M-C, Hantraye P, Dolan R, Palfi S, Maziere M, Brouillet E.Quantifiable bradykinesia, gait abnormalities and Huntington’s disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid. Neuroscience. 1997;79(1):45–56.</ref>
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;Scene #2: This is the ATP binding site. Upon the binding of phosphate to ADP, ATP is formed giving Kinesin the energy needed to move the cargo one step a head to its destination <scene name='75/752263/Atp_binding_site/5'> ATP-binding site </scene>
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== Structural highlights ==
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;Scene #3: This is the Microtubule-binding site, where Kinesin binds to microtubules for stability <scene name='75/752263/Mt-binding_site/1'> MT-binding site </scene>
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;Scene #4: some patients with CMT show mutation in the p-loop. A missense mutation results in a leucine in place of glutamine affecting signal transmission <scene name='75/752263/Cmt/1'> CMT </scene>
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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This is the structure of the yeast CsNMO. <scene name='75/752263/Alpha_beta_sheets/1'>This view</scene> shows the alpha helixes and beta pleated sheets of nitronate monooxygenase. There is eight parallel beta pleaded strands that are depicted in pink surrounded by eight alpha helixes in blue.
 
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FMN Binding site is formed with hydrogen bonds with main chain amino acids of G240, G261, and T262. <scene name='75/752263/Fmn_binding_site/1'>This is a view of the FMN Binding site with labeled amino acid residues.</scene>
 
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The phosphate group of FMN forms a hydrogen bond with the side-chain hydroxyl group of T262.
 
</StructureSection>
</StructureSection>
== References ==
== References ==
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#file:///C:/Users/Muna/Desktop/Spring%202021/Advanced%20Biochem/pcbi.1003329.pdf
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#https://www.ncbi.nlm.nih.gov/books/NBK22572/#:~:text=Kinesins%20moving%20along%20microtubules%20usually,surfaces%20of%20some%20eukaryotic%20cells.
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#https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Charcot-Marie-Tooth-Disease-Fact-Sheet
<references/>
<references/>

Current revision

Kinesin Motor Domain

Kinesin Protein

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References

  1. file:///C:/Users/Muna/Desktop/Spring%202021/Advanced%20Biochem/pcbi.1003329.pdf
  2. https://www.ncbi.nlm.nih.gov/books/NBK22572/#:~:text=Kinesins%20moving%20along%20microtubules%20usually,surfaces%20of%20some%20eukaryotic%20cells.
  3. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Charcot-Marie-Tooth-Disease-Fact-Sheet
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