Elucidation of inhibitor-binding pockets of d-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technologyElectronic supplementary information (ESI) available: Supplementary figures, NMR spectra, and PyMol session files of Fig. 2. See 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 in...
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Main Authors | , , , , , , , , , |
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Format | Journal Article |
Language | English |
Published |
27.06.2017
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Online Access | Get full text |
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Summary: | 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.
Binding pockets of a schizophrenia-related
d
-amino acid oxidase to its inhibitor were clarified by docking simulation and protein labeling experiments. |
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Bibliography: | Electronic supplementary information (ESI) available: Supplementary figures, NMR spectra, and PyMol session files of Fig. 2 See DOI 10.1039/c7ob00633k |
ISSN: | 1477-0520 1477-0539 |
DOI: | 10.1039/c7ob00633k |