D-Amino Acid Oxidase

A variety of anionic compounds was studied as inhibitors of d-amino acid oxidase by means of a recently described spectrophotometric assay for the enzyme. Several phosphorus- and sulfur-containing acids were shown not to be effective inhibitors of the enzyme. A series of meta- and para-substituted benzoic acid derivatives was studied as inhibitors and the σρ relationship obtained indicated the binding of these compounds to be facilitated by electron-withdrawing substituent groups. A variety of saturated and unsaturated carboxylic acids was evaluated as substrate-competitive inhibitors of the enzyme. It is indicated that these inhibitors interact with a positively charged group of the enzyme that is a critical distance from an aromatic residue contained in a limited nonpolar region of the enzyme. It is suggested that the aromatic residue of the protein interacts with the inhibitors through electron donation. Steric interactions involved in the binding of inhibitors were also observed.