Alternative Title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
Periodical titleInternational Journal of Molecular Sciences
Degree grantor/typeNagasaki University (長崎大学)
Note (General)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.
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
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
Citation: International Journal of Molecular Sciences, 22(15), 7830; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2022-03-18)
http://hdl.handle.net/10069/00041158
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2022-06-05T18:01:14+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション