Omega-amidase

Omega-amidase has two independent monomers that have structure organizations similar to other nitrilase enzymes found in bacteria. Each monomer has a four layered alpha/beta/beta/alpha conformation. Just as omega-amidase shares a general structure organization as other nitrilases, omega-amidase also contains the same catalytic triad within the active site. This triad of residues includes a nucleophilic cysteine, a glutamate base, and a lysine, all of which are conserved within the structure. == Mechanism ==

Omega amidase catalyzes the deamidation of several different alpha-keto acids into ammonia and metabolically useful carboxylic acids The general mechanism is the same as for other nitrilases: binding of the substrate to the active site, followed by release of ammonia, formation of a thioester intermediate at the cysteine, binding of water and then release of the carboxylic acid product. The catalytic triad glutamate transfers a proton to the amide group to create and release ammonia. The remaining thioester intermediate is stabilized by the lysine and the backbone amino group following the cysteine. This intermediate is attacked by water to form a stable tetrahedral intermediate. This intermediate breaks down to release the carboxylic acid and restore the enzyme. == Biology ==

Omega-amidase operates in coordination with glutamine transaminase to finish off the methionine salvage cycle in bacteria and plants. GTK catalyzes a reversible reaction, but coupling it with omega-amidase makes the transamination reaction irreversible at physiological conditions. Some such substrates are linked to diseases or conditions such as hyperammonemia. A list of some of the substrates that omega-amidase catalyzes may be found in Table 1. == Medical relevance ==

The NIT2 gene in humans has been found to be identical to omega-amidase. In addition to tumor suppression, NIT2/omega-amidase may be useful for detection and conversion of oncometabolites. Because omega-amidase is able to control concentration of toxic substrates such as KGM, it is likely that NIT2 can serve the same purpose. == References ==