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Biochemical Studies of Mitochondrial Malate:Quinone Oxidoreductase from Toxoplasma gondi
http://hdl.handle.net/10069/00041500
http://hdl.handle.net/10069/00041500c0de58ea-13a7-428d-a0ea-cf6a504b48e6
名前 / ファイル | ライセンス | アクション |
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ISYK1397_Acharjee.pdf (2.8 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2022-05-10 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Biochemical Studies of Mitochondrial Malate:Quinone Oxidoreductase from Toxoplasma gondi | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | toxoplasmosis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | electron transport chain | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | mitochondria | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | membrane protein | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | enzyme inhibition | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ferulenol | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
Acharjee, Rajib
× Acharjee, Rajib |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis and infects almost one-third of the global human population. A lack of effective drugs and vaccines and the emergence of drug resistant parasites highlight the need for the development of new drugs. The mitochondrial electron transport chain (ETC) is an essential pathway for energy metabolism and the survival of T. gondii. In apicomplexan parasites, malate:quinone oxidoreductase (MQO) is a monotopic membrane protein belonging to the ETC and a key member of the tricarboxylic acid cycle, and has recently been suggested to play a role in the fumarate cycle, which is required for the cytosolic purine salvage pathway. In T. gondii, a putative MQO (TgMQO) is expressed in tachyzoite and bradyzoite stages and is considered to be a potential drug target since its orthologue is not conserved in mammalian hosts. As a first step towards the evaluation of TgMQO as a drug target candidate, in this study, we developed a new expression system for TgMQO in FN102(DE3)TAO, a strain deficient in respiratory cytochromes and dependent on an alternative oxidase. This system allowed, for the first time, the expression and purification of a mitochondrial MQO family enzyme, which was used for steady-state kinetics and substrate specificity analyses. Ferulenol, the only known MQO inhibitor, also inhibited TgMQO at IC50 of 0.822 μM, and displayed different inhibition kinetics compared to Plasmodium falciparum MQO. Furthermore, our analysis indicated the presence of a third binding site for ferulenol that is distinct from the ubiquinone and malate sites. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1397号 学位授与年月日:令和4年3月18日 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Author: Rajib Acharjee, Keith K. Talaam, Endah D. Hartuti, Yuichi Matsuo, Takaya Sakura, Bundutidi M. Gloria, Shinya Hidano, Yasutoshi Kido, Mihoko Mori, Kazuro Shiomi, Masakazu Sekijima, Tomoyoshi Nozaki, Kousuke Umeda, Yoshifumi Nishikawa, Shinjiro Hamano, Kiyoshi Kita and Daniel K. Inaoka | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Citation: International Journal of Molecular Sciences, 22(15), 7830; 2021 | |||||
書誌情報 |
International Journal of Molecular Sciences 巻 22, 号 15, p. 7830, 発行日 2022-03-18 |
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EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1422-0067 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/ijms22157830 | |||||
権利 | ||||||
権利情報 | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
その他のタイトル | ||||||
その他のタイトル | トキソプラズマ原虫由来ミトコンドリア型リンゴ酸:キノン酸化還元酵素の生化学的解析 | |||||
出版者 | ||||||
出版者 | MDPI | |||||
関係URI | ||||||
識別子タイプ | HDL | |||||
関連識別子 | http://hdl.handle.net/10069/00041158 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17301 | |||||
学位授与機関名 | Nagasaki University (長崎大学) | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2022-03-18 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲医歯薬第1397号 | |||||
学位の種類 | ||||||
課程博士 | ||||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Nagasaki University (長崎大学), 博士(医学) (2022-03-18) |