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The C-terminal region of G72 increases D-amino acid oxidase activity.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2013 Dec 20; Vol. 15 (1), pp. 29-43. Date of Electronic Publication: 2013 Dec 20. - Publication Year :
- 2013
-
Abstract
- The schizophrenia-related protein G72 plays a unique role in the regulation of D-amino acid oxidase (DAO) in great apes. Several psychiatric diseases, including schizophrenia and bipolar disorder, are linked to overexpression of DAO and G72. Whether G72 plays a positive or negative regulatory role in DAO activity, however, has been controversial. Exploring the molecular basis of the relationship between G72 and DAO is thus important to understand how G72 regulates DAO activity. We performed yeast two-hybrid experiments and determined enzymatic activity to identify potential sites in G72 involved in binding DAO. Our results demonstrate that residues 123-153 and 138-153 in the long isoform of G72 bind to DAO and enhance its activity by 22% and 32%, respectively. A docking exercise indicated that these G72 peptides can interact with loops in DAO that abut the entrance of the tunnel that substrate and cofactor must traverse to reach the active site. We propose that a unique gating mechanism underlies the ability of G72 to increase the activity of DAO. Because upregulation of DAO activity decreases d-serine levels, which may lead to psychiatric abnormalities, our results suggest a molecular mechanism involving interaction between DAO and the C-terminal region of G72 that can regulate N-methyl-d-aspartate receptor-mediated neurotransmission.
- Subjects :
- Amino Acid Sequence
Binding Sites
Carrier Proteins chemistry
Carrier Proteins genetics
Catalytic Domain
D-Amino-Acid Oxidase chemistry
D-Amino-Acid Oxidase genetics
Intracellular Signaling Peptides and Proteins
Molecular Docking Simulation
Molecular Sequence Data
Mutation
Protein Isoforms chemistry
Protein Isoforms metabolism
Receptors, N-Methyl-D-Aspartate metabolism
Recombinant Proteins biosynthesis
Recombinant Proteins chemistry
Recombinant Proteins genetics
Serine metabolism
Two-Hybrid System Techniques
Carrier Proteins metabolism
D-Amino-Acid Oxidase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 24362575
- Full Text :
- https://doi.org/10.3390/ijms15010029