D-Amino acid oxidase: new findings.
The most recent research on D-amino acid oxidases and D-amino acid metabolism has revealed new, intriguing properties of the flavoenzyme and enlighted novel biotechnological uses of this catalyst. Concerning the in vivo function of the enzyme, new findings on the physiological role of D-amino acid oxidase point to a detoxifying function of the enzyme in metabolizing exogenous D-amino acids in animals. A novel role in modulating the level of D-serine in brain has also been proposed for the enzyme. At the molecular level, site-directed mutagenesis studies on the pig kidney D-amino acid oxidase and, more recently, on the enzyme from the yeast Rhodotorula gracilis indicated that the few conserved residues of the active site do not play a role in acid-base catalysis but rather are involved in substrate interactions. The three-dimensional structure of the enzyme was recently determined from two different sources: at 2.5-3.0 A resolution for DAAO from pig kidney and at 1.2-1.8 A resolution for R. gracilis. The active site can be clearly depicted: the striking absence of essential residues acting in acid-base catalysis and the mode of substrate orientation into the active site, taken together with the results of free-energy correlation studies, clearly support a hydrid transfer type of mechanism in which the orbital steering between the substrate and the isoalloxazine atoms plays a crucial role during catalysis.
Pilone
M S
MS
Department of Structural and Functional Biology, University of Insubria, Varese, Italy. mir@mailserver.unimi.it
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D003605:D-Amino-Acid Oxidase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D012248:Rhodotorula / Q000201:enzymology / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013053:Spectrophotometry; D013552:Swine
D003605:D-Amino-Acid Oxidase