The effect of fusidic acid on Plasmodium falciparum elongation factor G (EF-G)

Gupta, Ankit ; Mir, Snober S. ; Saqib, Uzma ; Biswas, Subir ; Vaishya, Suniti ; Srivastava, Kumkum ; Siddiqi, Mohammad Imran ; Habib, Saman (2013) The effect of fusidic acid on Plasmodium falciparum elongation factor G (EF-G) Molecular and Biochemical Parasitology, 192 (1-2). pp. 39-48. ISSN 0166-6851

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.molbiopara.2013.10.003

Abstract

Inhibition of growth of the malaria parasite Plasmodium falciparum by known translation-inhibitory antibiotics has generated interest in understanding their action on the translation apparatus of the two genome containing organelles of the malaria parasite: the mitochondrion and the relic plastid (apicoplast). We report GTPase activity of recombinant EF-G proteins that are targeted to the organelles and further use these to test the effect of the EF-G inhibitor fusidic acid (FA) on the factor–ribosome interface. Our results monitoring locking of EF-G·GDP onto surrogate Escherichia coli ribosomes as well as multi-turnover GTP hydrolysis by the factor indicate that FA has a greater effect on apicoplast EF-G compared to the mitochondrial counterpart. Deletion of a three amino acid (GVG) sequence in the switch I loop that is conserved in proteins of the mitochondrial EF-G1 family and the Plasmodium mitochondrial factor, but is absent in apicoplast EF-G, demonstrated that this motif contributes to differential inhibition of the two EF-Gs by FA. Additionally, the drug thiostrepton, that is known to target the apicoplast and proteasome, enhanced retention of only mitochondrial EF-G on ribosomes providing support for the reported effect of the drug on parasite mitochondrial translation.

Item Type:Article
Source:Copyright of this article belongs to Elsevier.
Keywords:Plasmodium falciparum; Fusidic Acid; Thiostrepton; Elongation Factor-G; Apicoplast; Mitochondria
ID Code:102068
Deposited On:09 Mar 2018 10:40
Last Modified:09 Mar 2018 10:40

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