Mutations in the pantothenate kinase of the malaria parasite P. falciparum confer resistance or hypersensitivity to diverse pantothenate analogues
نویسندگان
چکیده
1. Research School of Biology, The Australian National University, Canberra, Australia 2. Department of Chemistry, University of Glasgow, Glasgow, United Kingdom 3. Department of Chemistry, McGill University, Montreal, Quebec, Canada 4. Department of Biochemistry, Stellenbosch University, Matieland, South Africa 5. Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia 6. Department of Chemistry, Xi’an Jiaotong-Liverpool University, Suzhou, China 7. Medical School, The Australian National University, Canberra, Australia
منابع مشابه
Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues.
The malaria-causing blood stage of Plasmodium falciparum requires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation. Their mechanism ...
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Growth of the virulent human malaria parasite Plasmodium falciparum is dependent on an extracellular supply of pantothenate (vitamin B(5)) and is susceptible to inhibition by pantothenate analogues that hinder pantothenate utilization. In this study, on the hunt for pantothenate analogues with increased potency relative to those reported previously, we screened a series of pantothenamides (amid...
متن کاملH-coupled Pantothenate Transport in the Intracellular Malaria
Pantothenate, the precursor of coenzyme A, is an essential nutrient for the intraerythrocytic stage of the malaria parasite Plasmodium falciparum. Pantothenate enters the malaria-infected erythrocyte via new permeation pathways induced by the parasite in the host cell membrane (Saliba, K. J., Horner, H. A., and Kirk, K. (1998) J. Biol. Chem. 273, 10190–10195). We show here that pantothenate is ...
متن کاملH+-coupled pantothenate transport in the intracellular malaria parasite.
Pantothenate, the precursor of coenzyme A, is an essential nutrient for the intraerythrocytic stage of the malaria parasite Plasmodium falciparum. Pantothenate enters the malaria-infected erythrocyte via new permeation pathways induced by the parasite in the host cell membrane (Saliba, K. J., Horner, H. A., and Kirk, K. (1998) J. Biol. Chem. 273, 10190-10195). We show here that pantothenate is ...
متن کاملProvitamin B5 (pantothenol) inhibits growth of the intraerythrocytic malaria parasite.
Pantothenic acid, a precursor of the crucial enzyme cofactor coenzyme A, is one of a relatively few nutrients for which the intraerythrocytic parasite has an absolute and acute requirement from the external medium. In some organisms the provitamin pantothenol can serve as a source of pantothenic acid; however, this was not the case for the human malaria parasite Plasmodium falciparum. Instead, ...
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تاریخ انتشار 2017