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Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity
https://repo.qst.go.jp/records/47746
https://repo.qst.go.jp/records/47746fd4c3a41-1cd4-4340-abcb-97a745e18987
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-04-20 | |||||
| タイトル | ||||||
| タイトル | Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity | |||||
| 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 |
玉田, 太郎
× 玉田, 太郎× Waz, Shaimaa(熊本大学大学院薬学教育部)× 中村, 照也(熊本大学大学院薬学教育部)× 平田, 啓介(熊本大学大学院薬学教育部)× 古賀-小川, 由香里(日本医療科学大学)× 池鯉鮒, 麻美(熊本大学大学院薬学教育部)× 有森, 貴夫(大阪大学蛋白質研究所)× 池水, 信二(熊本大学大学院薬学教育部)× 中別府, 雄作(九州大学生体防御医学研究所)× 山縣, ゆり子(熊本大学大学院薬学教育部)× 玉田 太郎 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The human MutT homolog 1 (hMTH1, human NUDT1) hydrolyzes oxidatively damaged nucleoside triphosphates and is the main enzyme responsible for nucleotide sanitization. Here, we determined crystal structures of hMTH1 in complex with 8-oxo-dGTP or 2-oxo-dATP at neutral pH. These structures showed that the base moieties of two substrates are located on the similar but not the same position in the substrate-binding pocket and adopt a different hydrogen-bonding pattern. Analyses of bond lengths with high-resolution X-ray data and of the relation between the structure and enzymatic activity revealed that hMTH1 recognizes the different oxidized nucleotides via an exchange of the protonation state at two neighboring aspartate residues in its substrate-binding pocket. This mechanism of broad substrate recognition by enzymes has not been reported previously and may have relevance for anticancer drug development strategies targeting hMTH1. |
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| 書誌情報 |
The Journal of Biological Chemistry 巻 292, 号 7, p. 2785-2794, 発行日 2017-02 |
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| 出版者 | ||||||
| 出版者 | The American Society for Biochemistry and Molecular Biology, Inc. | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1074/jbc.M116.749713 | |||||
