Elucidation of inhibitor-binding pockets of D-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology

作者：Kohiki Taiki; Kato Yusuke; Nishikawa Yusuke; Yorita Kazuko; Sagawa Ikuko; Denda Masaya; Inokuma Tsubasa; Shigenaga Akira^*; Fukui Kiyoshi^*; Otaka Akira^*

来源：Organic and Biomolecular Chemistry, 2017, 15(25): 5289-5297.

DOI：10.1039/c7ob00633k

Because of the relevance of D-serine (D-Ser) to schizophrenia, inhibitors of D-amino acid oxidase (DAO), which catalyzes degradation of D-Ser in the presence of flavin adenine dinucleotide (FAD), are expected to be anti-schizophrenia therapeutics. In this study, binding pockets of DAO to its inhibitor 4-bromo-3-nitrobenzoic acid were searched by combining in silico docking simulation and labeling experiments employing an N-sulfanylethylanilide-based labeling technology that we have developed. The results clearly demonstrated that there are two binding pockets: one is shared with D-Ser and FAD, and the other is an unexpected cleft between the subunits of a DAO dimer. These findings will provide insight to aid the development of new DAO inhibitors. In addition, it was also proved that our labeling technology could be applicable to elucidate the binding pockets of proteins.

• 出版日期2017-7-7