ID 111927
Title Alternative
Elucidation of inhibitor-binding pocket of D-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology
Author
Kohiki, Taiki Tokushima University
Nishikawa, Yusuke Tokushima University
Denda, Masaya Tokushima University
Shigenaga, Akira Tokushima University|Japan Science and Technology Agency (JST) Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Content Type
Journal Article
Description
Because of 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 adeninde dinucleotide (FAD), are expected as 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 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 subunits of a DAO dimer. These findings will provide insight to aid the development of new hDAO inhibitors. In addition, it was also proved that our labeling technology could be applicable to elucidate the binding pockets of proteins.
Journal Title
Organic & Biomolecular Chemistry
ISSN
14770520
14770539
NCID
AA1168650X
AA12084375
Publisher
The Royal Society of Chemistry
Volume
15
Issue
25
Start Page
5289
End Page
5297
Published Date
2017-05-05
Rights
© The Royal Society of Chemistry 2017
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Institute of Advanced Medical Sciences
Technical Support Department
Pharmaceutical Sciences