Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodium falciparum plastid
Subir Biswas, Erin E Lim, Ankit Gupta, Uzma Saqib, Snober S Mir, Mohammad Imran Siddiqi, Stuart A Ralph, Saman Habib
INTERNATIONAL JOURNAL FOR PARASITOLOGY | ELSEVIER SCI LTD | Published : 2011
Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader seq..View full abstract
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Awarded by National Health and Medical Research Council, Australia
Awarded by European Community
We are grateful to Dr. Charlotte Knudsen (Aarhus University, Denmark) for the E. coli EF-Tu expression clone, Prof. Alan Cowman (Walter and Eliza Hall Institute, Australia) for the pGlux.1 vector, Prof. G.I. McFadden (University of Melbourne, Australia) for anti-ACP antibody, Prof. W.G.j. Hot (Howard Hughes Medical Institute, USA) for the RIG plasmid and Dr. P. Guptasarma (Institute of Microbial Technology, India) for help with stopped-flow fluorimetry. SB, AG and US received scholarships from the University Grants Commission and the Council for Scientific and Industrial Research, Government of India. SAR was funded by a CR Roper Fellowship from the University of Melbourne, Australia and National Health and Medical Research Council, Australia project grant 628704. This work has been conducted as part of the MEPHITIS project and partially funded by the European Community's Seventh Framework Programme (FP 7/2007-2013) under the grant agreement number HEALTH-F3-2009-223024. This is Central Drug Research Institute, India communication number 7897.