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Int. J. Mol. Sci. 2014, 15(1), 29-43; doi:10.3390/ijms15010029
Article

The C-Terminal Region of G72 Increases D-Amino Acid Oxidase Activity

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Received: 28 October 2013; in revised form: 28 November 2013 / Accepted: 6 December 2013 / Published: 20 December 2013
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
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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.
Keywords: D-amino acid oxidase; G72; yeast-two hybrid D-amino acid oxidase; G72; yeast-two hybrid
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Chang, S.L.-Y.; Hsieh, C.-H.; Chen, Y.-J.; Wang, C.-M.; Shih, C.-S.; Huang, P.-W.; Mir, A.; Lane, H.-Y.; Tsai, G.E.; Chang, H.-T. The C-Terminal Region of G72 Increases D-Amino Acid Oxidase Activity. Int. J. Mol. Sci. 2014, 15, 29-43.

AMA Style

Chang SL-Y, Hsieh C-H, Chen Y-J, Wang C-M, Shih C-S, Huang P-W, Mir A, Lane H-Y, Tsai GE, Chang H-T. The C-Terminal Region of G72 Increases D-Amino Acid Oxidase Activity. International Journal of Molecular Sciences. 2014; 15(1):29-43.

Chicago/Turabian Style

Chang, Sunny L.-Y.; Hsieh, Chia-Hung; Chen, Yen-Ju; Wang, Chien-Ming; Shih, Chung-Shiuan; Huang, Pei-Wen; Mir, Asif; Lane, Hsien-Yuan; Tsai, Guochuan E.; Chang, Hao-Teng. 2014. "The C-Terminal Region of G72 Increases D-Amino Acid Oxidase Activity." Int. J. Mol. Sci. 15, no. 1: 29-43.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert