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 [1]. NMO is widely known as the best system for P3N detoxification in many different organisms.
Function
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.[2][3] Recent structural studies suggest there are two classes of NMOs, Class I and Class II.[4] 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.[5]
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.[6]
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. [7] 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. [8]
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.[9]
Structural highlights
This is a sample scene created with SAT to by Group, and another to make 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 the structure of the yeast CsNMO. 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.
FMN Binding site is formed with hydrogen bonds with main chain amino acids of G240, G261, and T262.
