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A new target region for changing the substrate specificity of amine transaminases
http://hdl.handle.net/2261/57146
http://hdl.handle.net/2261/571469ea41bda-c0e0-4ea5-be42-762a6d7f4051
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
srep10753.pdf (1.9 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2015-07-30 | |||||
| タイトル | ||||||
| タイトル | A new target region for changing the substrate specificity of amine transaminases | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Protein design | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Biocatalysis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Transferases | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_6501 | |||||
| タイプ | journal article | |||||
| 著者 |
Guan, Li-Jun
× Guan, Li-Jun× Ohtsuka, Jun× Okai, Masahiko× Miyakawa, Takuya× Mase, Tomoko× Zhi, Yuehua× Hou, Feng× Ito, Noriyuki× Iwasaki, Akira× Yasohara, Yoshihiko× Tanokura, Masaru |
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| 著者所属 | ||||||
| 著者所属 | Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo | |||||
| 著者所属 | ||||||
| 著者所属 | Department of Ocean Sciences, Tokyo University of Marine Science and Technology | |||||
| 著者所属 | ||||||
| 著者所属 | Biotechnology Development Laboratories, Kaneka Corporation | |||||
| 著者所属 | ||||||
| 著者所属 | Research & Development Group, QOL Division, Kaneka Corporation | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | (R)-stereospecific amine transaminases (R-ATAs) are important biocatalysts for the production of (R)-amine compounds in a strict stereospecific manner. An improved R-ATA, ATA-117-Rd11, was successfully engineered for the manufacture of sitagliptin, a widely used therapeutic agent for type-2 diabetes. The effects of the individual mutations, however, have not yet been demonstrated due to the lack of experimentally determined structural information. Here we describe three crystal structures of the first isolated R-ATA, its G136F mutant and engineered ATA-117-Rd11, which indicated that the mutation introduced into the 136th residue altered the conformation of a loop next to the active site, resulting in a substrate-binding site with drastically modified volume, shape, and surface properties, to accommodate the large pro-sitagliptin ketone. Our findings provide a detailed explanation of the previously reported molecular engineering of ATA-117-Rd11 and propose that the loop near the active site is a new target for the rational design to change the substrate specificity of ATAs. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | UTokyo Research掲載「さまざまな薬の合成に重要な酵素が作用する相手を認識する仕組み」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/how-an-important-enzyme-used-in-drug-production-recognizes-its-substrate.html | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | UTokyo Research "How an important enzyme used in drug production recognizes its substrate" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/how-an-important-enzyme-used-in-drug-production-recognizes-its-substrate.html | |||||
| 書誌情報 |
Scientific Reports 巻 5, p. 10753, 発行日 2015-06-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2045-2322 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1038/srep10753 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Com- mons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | |||||
| 著者版フラグ | ||||||
| 値 | publisher | |||||
| 出版者 | ||||||
| 出版者 | Nature Publishing Group | |||||
| 関係URI | ||||||
| 関連タイプ | isReferencedBy | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.u-tokyo.ac.jp/focus/ja/articles/a_00408.html | |||||
| 関係URI | ||||||
| 関連タイプ | isReferencedBy | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.u-tokyo.ac.jp/focus/en/articles/a_00405.html | |||||
| 関係URI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1038/srep10753 | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
