Differential Kinetic Activities of Glycerol Kinase among African Trypanosome Species: Phylogenetic and Therapeutic Implications
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概要
- 論文の詳細を見る
African trypanosome species are causative agents for sleeping sickness in humans and nagana disease in cattle. Trypanosoma brucei can generate ATP via a reverse reaction with glycerol kinase (GK) when alternative oxidase (AOX) is inhibited; thus, GK is considered to be a crucial target for chemotherapy combined with AOX. However, the energy metabolism systems of African trypanosome species other than T. brucei are poorly understood. Thus, GK genes were surveyed from genome databases and cloned by PCR from T. vivax and T. congolense. Then, recombinant GK proteins (rGK) of T. vivax, T. congolense and T. brucei were expressed and purified. Kinetic analysis of these rGK proteins revealed that the Km values of T. congolense rGK for ADP and G-3-P substrates were lower than those of T. vivax and T. brucei. The expression level of GK molecules was highest in T. congolense cells and lowest in T. vivax cells. Based on these results, effective combination dosages of ascofuranone, a specific inhibitor of AOX, and glycerol, an inhibitor of the GK reverse reaction, were determined by using in vitro-cultured trypanosome cells.
著者
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Kita Kiyoshi
Department Of Biomedical Chemistry Graduate School Of Medicine The University Of Tokyo
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Ohshima Shigeru
Department Of Biomolecular Science Faculty Of Science Toho University
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Ohta Nobuo
Department Of Ent School Of Medicine Yamagata University
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Sakamoto Kimitoshi
Department Of Biomedical Chemistry Graduate School Of Medicine The University Of Tokyo
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Nakamura Kosuke
Department Of Biofunctional Chemistry Graduate School Of Natural Science And Technology Okayama Univ
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Yabu Yoshisada
Department Of Molecular Parasitology Nagoya City University Graduate School Of Medical Sciences
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Kido Yasutoshi
Department Of Biomedical Chemistry Graduate School Of Medicine The University Of Tokyo
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Suzuki Takashi
Department Of Anatomic Pathology Tohoku University School Of Medicine
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OHASHI-SUZUKI Mitsuko
Department of International Health Development, Division of Public Health, Graduate School of Tokyo Medical and Dental University
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OHSHIMA Shigeru
Department of Core Laboratory, Nagoya City University Graduate School of Medical Sciences
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