Aspartoacylase
![Structure of aspartoacylase dimer. Generated from 2I3C.[1]](/uploads/202412/22/ASPA_dimer4237.png)
![A monomer of aspartoacylase with the N-domain in green, C-domain in yellow, and zinc cofactor in red. Generated from 2I3C.[1]](/uploads/202412/22/ASPA_domains4237.png)
![Active site of aspartoacylase with a bound N-phosphonamidate-L-aspartate. This is a tetrahedral intermediate analogue with phosphorus replacing the attacked carbon. In the structure, zinc, Arg-63, and Glu-178 are stabilizing the tetrahedral intermediate. Generated from 2O4H.[8]](/uploads/202412/22/ASPA_bound_to_an_intermediate_analogue4237.png)
![Aspartoacylase mechanism.[8] All the coordinating residues are not shown for clarity.](/uploads/202412/22/ASPA_mechanism4237.jpg)
Aspartoacylase (EC3.5.1.15, aminoacylase II, N-acetylaspartate amidohydrolase, acetyl-aspartic deaminase, acylase II, ASPA) is a hydrolase enzyme responsible for catalyzing the deacylation of N-acetyl-l-aspartate (N-acetylaspartate,NAA) into aspartate and acetate. It is a zinc-dependent hydrolase that promotes the deprotonation of water to use as a nucleophile in a mechanism analogous to many other zinc-dependent hydrolases. It is most commonly found in the brain, where it controls the levels of N-actetyl-l-aspartate. Mutations that result in loss of aspartoacylase activity are associated with Canavan disease, a rare autosomal recessive neurodegenerative disorder.