{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:17:08Z","timestamp":1780510628791,"version":"3.54.1"},"reference-count":94,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Infectious Disease Control from the Science and Technology Research Partnership for Sustainable Development (SATREPS)","award":["10000284"],"award-info":[{"award-number":["10000284"]}]},{"name":"Infectious Disease Control from the Science and Technology Research Partnership for Sustainable Development (SATREPS)","award":["14425718"],"award-info":[{"award-number":["14425718"]}]},{"name":"Japanese Initiative for Progress of Research on Infectious Diseases for Global Epidemics","award":["JP18fm0208027"],"award-info":[{"award-number":["JP18fm0208027"]}]},{"name":"Japanese Initiative for Progress of Research on Infectious Diseases for Global Epidemics","award":["JP18fm0208020"],"award-info":[{"award-number":["JP18fm0208020"]}]},{"name":"Grant-in-aid for Scientific Research on Priority Areas","award":["18073004"],"award-info":[{"award-number":["18073004"]}]},{"name":"Creative Scientific Research Grant","award":["18GS0314"],"award-info":[{"award-number":["18GS0314"]}]},{"name":"Grants-in-aid for Scientific Research (A)","award":["20H00620"],"award-info":[{"award-number":["20H00620"]}]},{"name":"Grants-in-aid for Scientific Research (B)","award":["16K19114"],"award-info":[{"award-number":["16K19114"]}]},{"name":"Grants-in-aid for Scientific Research (B)","award":["19H03436"],"award-info":[{"award-number":["19H03436"]}]},{"name":"Grants-in-aid for Scientific Research (C)","award":["19K07523"],"award-info":[{"award-number":["19K07523"]}]},{"name":"The Leading Initiative for Excellent Young Researchers (LEADER)","award":["16811362"],"award-info":[{"award-number":["16811362"]}]},{"name":"Grants-in-aid for Research on Emerging and Re-emerging Infectious Diseases","award":["17929833"],"award-info":[{"award-number":["17929833"]}]},{"name":"Grants-in-aid for Research on Emerging and Re-emerging Infectious Diseases","award":["20314363"],"award-info":[{"award-number":["20314363"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03bcM, 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.<\/jats:p>","DOI":"10.3390\/ijms22157830","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T22:35:31Z","timestamp":1626993331000},"page":"7830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biochemical Studies of Mitochondrial Malate: Quinone Oxidoreductase from Toxoplasma gondii"],"prefix":"10.3390","volume":"22","author":[{"given":"Rajib","family":"Acharjee","sequence":"first","affiliation":[{"name":"Program for Nurturing Global Leaders in Tropical and Emerging Communicable Disease, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Zoology, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-3648","authenticated-orcid":false,"given":"Keith","family":"Talaam","sequence":"additional","affiliation":[{"name":"Program for Nurturing Global Leaders in Tropical and Emerging Communicable Disease, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endah","family":"Hartuti","sequence":"additional","affiliation":[{"name":"Program for Nurturing Global Leaders in Tropical and Emerging Communicable Disease, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Laboratory for Biotechnology, Agency for the Assessment and Application of Technology, South Tangerang 15314, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Graduate School of Life Science, Kumamoto University, Kumamoto 860-0862, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-8485","authenticated-orcid":false,"given":"Takaya","family":"Sakura","sequence":"additional","affiliation":[{"name":"School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bundutidi","family":"Gloria","sequence":"additional","affiliation":[{"name":"Program for Nurturing Global Leaders in Tropical and Emerging Communicable Disease, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Pediatric, Kinshasa University Hospital, University of Kinshasa, Kinshasa P.O. Box 123, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Hidano","sequence":"additional","affiliation":[{"name":"Department of Immune Regulation, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-2631","authenticated-orcid":false,"given":"Yasutoshi","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoko","family":"Mori","sequence":"additional","affiliation":[{"name":"Biological Resource Center, NITE, Kisarazu, Chiba 292-0818, Japan"},{"name":"Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-0072, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-5116","authenticated-orcid":false,"given":"Kazuro","family":"Shiomi","sequence":"additional","affiliation":[{"name":"Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-0072, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3806-9535","authenticated-orcid":false,"given":"Masakazu","family":"Sekijima","sequence":"additional","affiliation":[{"name":"Department of Advanced Computational Drug Discovery Unit, Tokyo Institute of Technology, Yokohama 226-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1354-5133","authenticated-orcid":false,"given":"Tomoyoshi","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousuke","family":"Umeda","sequence":"additional","affiliation":[{"name":"Pathology Division, Aquaculture Research Department, Fisheries Technology Institute, Japan Fisheries Research and Education Agency, Minamiise 516-0193, Japan"},{"name":"Research Unit for Host Defense, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5005-6377","authenticated-orcid":false,"given":"Yoshifumi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Research Unit for Host Defense, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3881-8337","authenticated-orcid":false,"given":"Shinjiro","family":"Hamano","sequence":"additional","affiliation":[{"name":"Program for Nurturing Global Leaders in Tropical and Emerging Communicable Disease, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"The Joint Usage\/Research Center on Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Kita","sequence":"additional","affiliation":[{"name":"School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"},{"name":"Department of Host-Defense Biochemistry, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9791-927X","authenticated-orcid":false,"given":"Daniel","family":"Inaoka","sequence":"additional","affiliation":[{"name":"School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan"},{"name":"Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1086\/521246","article-title":"Fatal outbreak of human toxoplasmosis along the Maroni River: Epidemiological, clinical, and parasitological aspects","volume":"45","author":"Demar","year":"2007","journal-title":"Clin. 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