Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase

Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase

D-amino acid oxidase (DAAO) catalyzes the oxidative deamination of several neutral D-amino acids and is the enzyme mainly responsible (together with serine racemase) for degrading D-serine (D-Ser) in the central nervous system of mammals. This D-amino acid, which binds the coagonist site of the N-methyl-D-aspartate receptor, is thus a key neuromodulator of glutamatergic neurotransmission. Alter...

Flavoenzyme catalysis: substrate-competitive inhibition of D-amino acid oxidase.

In an earlier paper from this laboratory (1) there were described the characteristics of competitive inhibition resulting from the interference of certain aromatic compounds with the association of flavin adenine dinucleotide and the separated protein of n-amino acid oxidase. Included among the inhibitors were auramine, quinine, and various other quinolines and anilines. We now present our find...

The Therapeutic Potential of D-Amino Acid Oxidase (DAAO) Inhibitors

D-amino acid oxidase (DAAO) is a flavoenzyme that degrades D-amino acids through the process of oxidative deamination. DAAO regulation of D-amino acid levels has been associated with several physiological processes ranging from hormone secretion to synaptic transmission and cognition. Recent genetic studies have identified a mutation on chromosome 13 in schizophrenia patients that encodes two g...

Astudyon D-amino-acid Oxidase

Novel human D-amino acid oxidase inhibitors stabilize an active-site lid-open conformation

The NMDAR (N-methyl-D-aspartate receptor) is a central regulator of synaptic plasticity and learning and memory. hDAAO (human D-amino acid oxidase) indirectly reduces NMDAR activity by degrading the NMDAR co-agonist D-serine. Since NMDAR hypofunction is thought to be a foundational defect in schizophrenia, hDAAO inhibitors have potential as treatments for schizophrenia and other nervous system ...