The C-terminal region of G72 increases D-amino acid oxidase activity

International Journal of Molecular Sciences
Sunny Li-Yun ChangHao-Teng Chang

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 DA...Continue Reading

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Citations

Aug 1, 2014·Cellular and Molecular Neurobiology·David-Marian OtteAndreas Zimmer
Nov 6, 2015·BioMed Research International·Maofeng WangHao-Teng Chang
Feb 7, 2017·FEBS Letters·Silvia SacchiLoredano Pollegioni
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Jun 9, 2017·Scientific Reports·Qingju LiuYujian He

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Methods Mentioned

BETA
two-hybrid
pull-down
biopsies
confocal
Fluorescence
PCR
electrophoresis

Software Mentioned

ClusPro
MODELLER
HNN

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