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

IR@CDRI: CSIR-Central Drug Research Institute, Lucknow


Field	Value

Creator	Gupta, Ankit Mir, S S Saqib, Uzma Biswas, Subir Vaishya, Suniti Srivastava, Kumkum Siddiqi, M I Habib, Saman

Date	2014-05-09T07:22:02Z 2014-05-09T07:22:02Z 2013

Identifier	Molecular & Biochemical Parasitology2013, 192, 39– 48 http://hdl.handle.net/123456789/1217

Description	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 E. 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.

Format	678791 bytes application/pdf

Language	en

Relation	CSIR-CDRI communication no. 8561

Subject	Effect Fusidic Plasmodium Falciparum Longation Factor G (EF-G)

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

Type	Article