Human D-Amino Acid Oxidase: Structure, Function, and Regulation
TLDR
The known properties of human DAAO suggest that its activity must be finely tuned to fulfill a main physiological function such as the control of D-serine levels in the brain as well as the role of post-translational modifications on its main biochemical properties at the cellular level.Abstract:
D-Amino acid oxidase (DAAO) is an FAD-containing flavoenzyme that catalyzes with absolute stereoselectivity the oxidative deamination of all natural D-amino acids, the only exception being the acidic ones. This flavoenzyme plays different roles during evolution and in different tissues in humans. Its three-dimensional structure is well conserved during evolution: minute changes are responsible for the functional differences between enzymes from microorganism sources and those from humans. In recent years several investigations focused on human DAAO, mainly because of its role in degrading the neuromodulator D-serine in the central nervous system. D-Serine is the main coagonist of N-methyl D-aspartate receptors, i.e., excitatory amino acid receptors critically involved in main brain functions and pathologic conditions. Human DAAO possesses a weak interaction with the FAD cofactor; thus, in vivo it should be largely present in the inactive, apoprotein form. Binding of active-site ligands and the substrate stabilizes flavin binding, thus pushing the acquisition of catalytic competence. Interestingly, the kinetic efficiency of the enzyme on D-serine is very low. Human DAAO interacts with various proteins, in this way modulating its activity, targeting, and cell stability. The known properties of human DAAO suggest that its activity must be finely tuned to fulfill a main physiological function such as the control of D-serine levels in the brain. At present, studies are focusing on the epigenetic modulation of human DAAO expression and the role of post-translational modifications on its main biochemical properties at the cellular level.read more
Citations
More filters
Journal ArticleDOI
Colorimetric quantification of sodium benzoate in food by using d-amino acid oxidase and 2D metal organic framework nanosheets mediated cascade enzyme reactions
TL;DR: In this paper , a rapid colorimetric method for detecting sodium benzoate in food products was established based on the d-amino acid oxidase (DAAO) and 2D metal organic framework (2D MOF) mediated cascade enzyme reactions.
Journal ArticleDOI
Results of a randomized double-blind study evaluating luvadaxistat in adults with Friedreich ataxia
Hao Wang,Jonathan D. Norton,Lin Xu,Nicholas DeMartinis,Rohini Sen,Ankit Shah,Jennifer Farmer,David A. Lynch,David A. Lynch +8 more
TL;DR: In this paper, Luvadaxistat was shown to be safe and well tolerated in this cohort of adults with Friedreich ataxia; however, it did not demonstrate efficacy as a treatment for this condition.
Journal ArticleDOI
Chiral resolution of plasma amino acids reveals enantiomer-selective associations with organ functions
TL;DR: Chiral resolution of plasma amino acids revealed totally different associations of the enantiomers with organ functions, and warrants further investigation for clinical and laboratory usefulness.
Journal ArticleDOI
Coumarin derivatives as inhibitors of d-amino acid oxidase and monoamine oxidase.
TL;DR: In this paper , a series of synthetic and commercially available coumarin derivatives were evaluated as potential MAO inhibitors, and a number of high potency inhibitors were identified, with the most potent inhibitors being 3,7-dihydroxycoumarin with an IC50 values of 0.167 and 0.224 µM, respectively.
References
More filters
Journal ArticleDOI
Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity
TL;DR: The major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain are reviewed, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors.
Journal ArticleDOI
Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis
TL;DR: Hypofunction of the NMDA receptor, possibly on critical GABAergic inter-neurons, may contribute to the pathophysiology of schizophrenia.
Journal ArticleDOI
BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology.
TL;DR: The first update of BindingDB since 2007 is provided, focusing on new and unique features and highlighting directions of importance to the field as a whole.
Journal ArticleDOI
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Elizabeth T. Cirulli,Brittany N. Lasseigne,Slavé Petrovski,Peter C. Sapp,Patrick A. Dion,Claire S. Leblond,Julien Couthouis,Yi-Fan Lu,Quanli Wang,Brian J. Krueger,Zhong-fa Ren,Jonathan E. M. Keebler,Yujun Han,Shawn Levy,Braden E. Boone,Jack R. Wimbish,Lindsay L. Waite,Angela Jones,John P. Carulli,Aaron G. Day-Williams,John F. Staropoli,Winnie Xin,Alessandra Chesi,Alya R. Raphael,Diane McKenna-Yasek,Janet Cady,J. M. B. Vianney de Jong,Kevin P. Kenna,Bradley N. Smith,Simon Topp,Jack W. Miller,Athina-Soragia Gkazi,Ammar Al-Chalabi,Leonard H. van den Berg,Jan H. Veldink,Vincenzo Silani,Nicola Ticozzi,Christopher Shaw,Robert H. Baloh,Stanley H. Appel,Ericka Simpson,Clotilde Lagier-Tourenne,Stefan M. Pulst,Summer Gibson,John Q. Trojanowski,Lauren Elman,Leo McCluskey,Murray Grossman,Neil A. Shneider,Wendy K. Chung,John Ravits,Jonathan D. Glass,Katherine B. Sims,Vivianna M. Van Deerlin,Tom Maniatis,Sebastian D. Hayes,Alban Ordureau,Sharan Swarup,John Landers,Frank Baas,Andrew S. Allen,Richard Bedlack,J. Wade Harper,Aaron D. Gitler,Guy A. Rouleau,Robert H. Brown,Matthew B. Harms,Gregory M. Cooper,Tim Harris,Richard M. Myers,David Goldstein +70 more
TL;DR: A moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS found several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene.
Journal ArticleDOI
Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia.
Ilya Chumakov,Marta Blumenfeld,Oxana Guerassimenko,Laurent Cavarec,Marta Palicio,Hadi Abderrahim,Lydie Bougueleret,C Barry,Hiroaki Tanaka,Philippe La Rosa,Anne Puech,Nadia Tahri,Annick Cohen-Akenine,Sylvain Delabrosse,Sébastien Lissarrague,Françoise-Pascaline Picard,Karelle Maurice,Laurent Essioux,Philippe Millasseau,Pascale Grel,Virginie Debailleul,Anne-Marie Simon,Dominique Caterina,Isabelle Dufaure,Kattayoun Malekzadeh,Maria Belova,Jian-Jian Luan,Michel Bouillot,Jean-Luc Sambucy,Gwenael Primas,Martial Saumier,Nadia Boubkiri,Sandrine Martin-Saumier,Myriam Nasroune,Hélène Peixoto,A Delaye,Virginie Pinchot,Mariam Bastucci,Sophie Guillou,Magali Chevillon,Ricardo Sainz-Fuertes,Said Meguenni,Joan Aurich-Costa,Dorra Cherif,Anne Gimalac,Cornelia M. van Duijn,Denis Gauvreau,Gail Ouelette,Isabel Fortier,John Realson,Tatiana Sherbatich,Nadejda Riazanskaia,Evgeny I. Rogaev,Peter Raeymaekers,Jeroen Aerssens,Frank Konings,Walter Luyten,Fabio Macciardi,Pak C. Sham,Richard E. Straub,Daniel R. Weinberger,Nadine Cohen,Daniel Cohen +62 more
TL;DR: A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia, pointing to the involvement of this N-methyl-d-aspartate receptor regulation pathway in schizophrenia.