Structure models of G72, the product of a susceptibility gene to schizophrenia.
The G72 gene is one of the most susceptible genes to schizophrenia and is contained exclusively in the genomes of primates. The product of the G72 gene modulates the activity of D-amino acid oxidase (DAO) and is a small protein prone to aggregate, which hampers its structural studies. In addition, lack of a known structure of a homologue makes it difficult to use the homology modelling method for the prediction of the structure. Thus, we first developed a hybrid ab initio approach for small proteins prior to the prediction of the structure of G72. The approach uses three known ab initio algorithms. To evaluate the hybrid approach, we tested our prediction of the structure of the amino acid sequences whose structures were already solved and compared the predicted structures with the experimentally solved structures. Based on these comparisons, the average accuracy of our approach was calculated to be ∼5 Å. We then applied the approach to the sequence of G72 and successfully predicted the structures of the N- and C-terminal domains (ND and CD, respectively) of G72. The predicted structures of ND and CD were similar to membrane-bound proteins and adaptor proteins, respectively.
Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
Yusuke
Y
Kato
Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
Kiyoshi
K
Fukui
D000465:Algorithms; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D056004:Molecular Dynamics Simulation; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism
D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins
D-amino acid oxidase; G72; ab initio method; schizophrenia; structure prediction