| Property | Value |
|---|---|
| Protein Name | D-Amino Acid Oxidase |
| Gene | DAO/DAOA |
| UniProt ID | O00327 |
| Molecular Weight | ~40 kDa |
| Subcellular Localization | Peroxisomes |
| Protein Family | FAD-dependent oxidoreductases |
D-Amino Acid Oxidase (DAO/DAOA) is a flavin adenine dinucleotide (FAD)-dependent enzyme that catalyzes the oxidative deamination of D-amino acids[1]. It has gained significant attention in neuroscience due to its proposed role in modulating NMDA receptor signaling and its genetic association with schizophrenia and other neuropsychiatric disorders.
DAO contains characteristic structural features essential for its enzymatic function:
FAD-binding domain: The N-terminal region (approximately 30-200 amino acids) contains the binding site for the flavin adenine dinucleotide cofactor. This domain adopts a characteristic Rossmann-like fold that stabilizes the FAD molecule through hydrogen bonds and hydrophobic interactions[2].
Active site: The central region forms the substrate-binding pocket that recognizes the D-stereoisomer of amino acids. The active site contains key catalytic residues including a conserved serine, tyrosine, and glutamate that participate in the oxidative deamination reaction.
Peroxisomal targeting signal: The C-terminal region contains the tripeptide SKL (serine-lysine-leucine) peroxisomal targeting signal (PTS1), which directs the enzyme to peroxisomes.
Dimerization interface: DAO forms functional homodimers, with each monomer capable of independently binding FAD and substrate.
DAO catalyzes the oxidative deamination of D-amino acids:
D-amino acid + O2 + H2O → 2-oxo acid + NH3 + H2O2
The reaction proceeds through a reductive half-reaction where the substrate reduces the flavin, followed by an oxidative half-reaction where the reduced flavin is reoxidized by molecular oxygen, producing hydrogen peroxide as a byproduct.
DAO shows broad specificity for D-amino acids:
DAO plays a crucial role in D-amino acid catabolism:
In the central nervous system, DAO modulates neurotransmission through:
DAO/DAOA is one of the most extensively studied schizophrenia risk genes[3][4]:
Several DAO inhibitors have been developed as potential therapeutics:
Pollegioni, L. & Piubelli, L. (2007). D-amino acid oxidase: physiological role and applications. FEBS Journal, 274(S1), 2630. 2007. ↩︎
Pawlowski, M. et al. (2001). The crystal structure of D-amino acid oxidase at very high resolution. Journal of Molecular Biology, 307(1), 171-188. 2001. ↩︎
Lin, C.H. et al. (2014). D-amino acid oxidase and schizophrenia. Current Medicinal Chemistry, 21(12), 1344-1359. 2014. ↩︎
Rogaeva, E. & St George-Hyslop, P.H. (2007). Genetic evidence for a novel susceptibility gene for schizophrenia. Nature Genetics, 39(2), 139-140. 2007. ↩︎