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P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency.
https://repo.qst.go.jp/records/81703
https://repo.qst.go.jp/records/8170388ef156e-4f97-481f-8263-5227b81b6984
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-01-20 | |||||
| タイトル | ||||||
| タイトル | P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Rachadech, Wanitcha
× Rachadech, Wanitcha× Kato, Yusuke× Rabab, M Abou El-Magd× Shishido, Yuji× Hyeon Kim, Soo× Sogabe, Hirofumi× Maita, Nobuo× Yorita, Kazuko× Fukui, Kiyoshi× Nobuo, Maita |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7-0.9 µM) compared with wild-type (1.2-2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure-function relationship of human DAO. | |||||
| 書誌情報 |
Journal of biochemistry 巻 168, 号 5, p. 557-567-567, 発行日 2020-11 |
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| 出版者 | ||||||
| 出版者 | Oxford University Press | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0021-924X | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 32730563 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/jb/mvaa083 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://academic.oup.com/jb/article/168/5/557/5878969 | |||||
