Elucidation of inhibitor-binding pockets of d-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology. Issue 25 (16th May 2017)

• Record Type: Journal Article
• Authors: Kohiki, Taiki; Kato, Yusuke; Nishikawa, Yusuke; Yorita, Kazuko; Sagawa, Ikuko; Denda, Masaya; Inokuma, Tsubasa; Shigenaga, Akira; Fukui, Kiyoshi; Otaka, Akira
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 25(2017)
• Page Start: 5289
• Page End: 5297
• Publication Date: 2017-05-16
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob00633k
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Binding pockets of a schizophrenia-relatedd -amino acid oxidase to its inhibitor were clarified by docking simulation and protein labeling experiments. Abstract : Because of the relevance ofd -serine (d -Ser) to schizophrenia, inhibitors ofd -amino acid oxidase (DAO), which catalyzes degradation ofd -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 withd -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.