ArticleProtein science : a publication of the Protein Society2006
Crystal structure of human D-amino acid oxidase: context-dependent variability of the backbone conformation of the VAAGL hydrophobic stretch located at the si-face of the flavin ring.
Article in Protein science : a publication of the Protein Society, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 107 citations in OpenAlex.
- Blood levels of D-aspartate oxidase, D-amino acid oxidase, serine racemase, and pLG72 are influenced by diagnoses of schizophrenia and autism spectrum disorder.Schizophrenia (Heidelberg, Germany) · 2026Article
- Crystal structure of D-aspartate oxidase from Cryptococcus humicola UJ1.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Cavity-Based Discovery of New Fatty Acid Photodecarboxylases.Chembiochem : a European journal of chemical biology · 2024Article
- Review
- On the regulation of human D-aspartate oxidase.Protein science : a publication of the Protein Society · 2023Article
- Studying the interaction between PEX5 and its full-length cargo proteins in living cells by a novel Försteŕs resonance energy transfer-based competition assay.Frontiers in cell and developmental biology · 2022Article
- Human D-aspartate Oxidase: A Key Player in D-aspartate Metabolism.Frontiers in molecular biosciences · 2021Article
- Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia.Frontiers in psychiatry · 2021Review
- X-ray structure analysis of a unique D-amino-acid oxidase from the thermophilic fungus Rasamsonia emersonii strain YA.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Mechanistic insights into the loss-of-function mechanisms of rare human D-amino acid oxidase variants implicated in amyotrophic lateral sclerosis.Scientific reports · 2020Article
- Enzymatic determination of D-alanine using a cationic poly(fluorenylenephenylene) as the fluorescent probe and MnO2 nanosheets as quenchers.Mikrochimica acta · 2019Article
- Substitution of Arginine 120 in Human D-Amino Acid Oxidase Favors FAD-Binding and Nuclear Mistargeting.Frontiers in molecular biosciences · 2019Article
- Structural basis for potent inhibition of d-amino acid oxidase by thiophene carboxylic acids.European journal of medicinal chemistry · 2018Article
- Human D-Amino Acid Oxidase: Structure, Function, and Regulation.Frontiers in molecular biosciences · 2018Review
- Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access.PloS one · 2018Article
- Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential Significance in Pathologies.Frontiers in molecular biosciences · 2018Review
- Focus on the Role of D-serine and D-amino Acid Oxidase in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS).Frontiers in molecular biosciences · 2018Review
- Assessment of the Target Engagement and D-Serine Biomarker Profiles of the D-Amino Acid Oxidase Inhibitors Sodium Benzoate and PGM030756.Neurochemical research · 2017Article
- Assays of D-Amino Acid Oxidase Activity.Frontiers in molecular biosciences · 2017Article
- Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase.Frontiers in molecular biosciences · 2017Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the brain, the extensively studied FAD-dependent enzyme D-amino acid oxidase (DAO) degrades the gliotransmitter D-serine, a potent activator of N-methyl-D-aspartate type glutamate receptors, and evidence suggests that DAO, together with its activator G72 protein, may play a key role in the pathophysiology of schizophrenia. Indeed, its potential clinical importance highlights the need for structural and functional analyses of human DAO. We recently succeeded in purifying human DAO, and found that it weakly binds FAD and shows a significant slower rate of flavin reduction compared with porcine DAO. However, the molecular basis for the different kinetic features remains unclear because the active site of human DAO was considered to be virtually identical to that of porcine DAO, as would be expected from the 85% sequence identity. To address this issue, we determined the crystal structure of human DAO in complex with a competitive inhibitor benzoate, at a resolution of 2.5 Angstrom. The overall dimeric structure of human DAO is similar to porcine DAO, and the catalytic residues are fully conserved at the re-face of the flavin ring. However, at the si-face of the flavin ring, despite the strict sequence identity, a hydrophobic stretch (residues 47-51, VAAGL) exists in a significantly different conformation compared with both of the independently determined porcine DAO-benzoate structures. This suggests that a context-dependent conformational variability of the hydrophobic stretch accounts for the low affinity for FAD as well as the slower rate of flavin reduction, thus highlighting the unique features of the human enzyme.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.