The Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily belongs to the M14 family of metallocarboxypeptidases (MCPs), and includes ASTE, which catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-2; EC:3.5.1.15) which cleaves N-acetyl L-aspartic acid (NAA) into aspartate and acetate. NAA is abundant in the brain, and hydrolysis of NAA by ASPA may help maintain white matter. ASPA is an NAA scavenger in other tissues. Mutations in the gene encoding ASPA cause Canavan disease (CD), a fatal progressive neurodegenerative disorder involving dysmyelination and spongiform degeneration of white matter in children. This enzyme binds zinc which is necessary for activity. Measurement of elevated NAA levels in urine is used in the diagnosis of CD.
Comment:Metallocarboxypeptidases share the zinc binding motif HXXE...H, where the zinc ion is penta-coordinated to ND1 atoms of the histidines, OE1 and OE2 atoms of the glutamic acid, and to a water molecule in a slightly distorted tetrahedral manner.
Structure:1YW4_A: Chromobacterium violaceum succinylglutamate desuccinylase bound to zinc; contacts at 3.5A
Structure:2O4H_A: human brain aspartoacylase bound to zinc; contacts at 3.5A
Jiyao W et al.(2023). "The conserved domain database in 2023.",