Project Summary

Dominika Borek, Ph.D. (Young Investigator 2005) of the University of Texas Southwestern Medical Center at Dallas, plans to characterize via x-ray crystallography and other methods the structure of G72, a protein that activates D-serine oxidation by D-amino acid oxidase (DAAO), mutations in which have been linked to schizophrenia. Excessive D-serine metabolism results in disturbed glutamate signaling, which may contribute to schizophrenia. G72 also has been implicated in bipolar disease. The proposed studies will characterize the interactions between DAAO and G72 using a variety of methods. X-ray crystallography will identify the atomic structure of G72 and its complex with DAAO. G72 mutants will be analyzed for their effect on DAAO activity. Analytical ultracentrifugation will determine subunits of G72 and thermal analysis will measure the stability of the protein and its interaction with other molecules. The detailed description of G72 and the DAAO-G72 complex will provide a better understanding of the biochemical events contributing to schizophrenia and bipolar disorder. The findings may provide a stimulus for new drugs that stabilize brain executive function.

Program Area: MULTIPLE FOCUS AREAS\Bipolar Disorder/Schizophrenia

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