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Diverse substrate recognition and hydrolysis mechanisms of human NUDT5
http://hdl.handle.net/2298/25701
http://hdl.handle.net/2298/2570106814e2c-b415-4e1a-b20e-1d3150bb4a88
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
8972full.pdf
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| Item type | 一般雑誌記事 / Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-10-15 | |||||
| タイトル | ||||||
| タイトル | Diverse substrate recognition and hydrolysis mechanisms of human NUDT5 | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
Arimori, Takao
× Arimori, Takao× Tamaoki, Haruhiko× Nakamura, Teruya× Kamiya, Hiroyuki× Ikemizu, Shinji× Takagi, Yasumitsu× Ishibashi, Toru× Harashima, Hideyoshi× Sekiguchi, Mutsuo× Yamagata, Yuriko |
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| 内容記述 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Human NUDT5 (hNUDT5) hydrolyzes various modified nucleoside diphosphates including 8-oxo-dGDP, 8-oxo-dADP and ADP-ribose (ADPR). However, the structural basis of the broad substrate specificity remains unknown. Here, we report the crystal structures of hNUDT5 complexed with 8-oxo-dGDP and 8-oxo-dADP. These structures reveal an unusually different substrate-binding mode. In particular, the positions of two phosphates (α and β phosphates) of substrate in the 8-oxo-dGDP and 8-oxo-dADP complexes are completely inverted compared with those in the previously reported hNUDT5–ADPR complex structure. This result suggests that the nucleophilic substitution sites of the substrates involved in hydrolysis reactions differ despite the similarities in the chemical structures of the substrates and products. To clarify this hypothesis, we employed the isotope-labeling method and revealed that 8-oxo-dGDP is attacked by nucleophilic water at Pβ, whereas ADPR is attacked at Pα. This observation reveals that the broad substrate specificity of hNUDT5 is achieved by a diversity of not only substrate recognition, but also hydrolysis mechanisms and leads to a novel aspect that enzymes do not always catalyze the reaction of substrates with similar chemical structures by using the chemically equivalent reaction site. | |||||
| bibliographic_information |
en : Nucleic Acids Research 巻 39, 号 20, p. 8972-8983, 発行日 2011-11 |
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| item_24_source_id_7 | ||||||
| 収録物識別子 | 1362-4962 | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 490 | |||||
| 出版者 | ||||||
| 出版者 | Oxford University Press | |||||
| 言語 | en | |||||
| 関連 | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1093/nar/gkr575 | |||||
