tailieunhanh - Báo cáo khoa học: Helicases ) feasible antimalarial drug target for Plasmodium falciparum

Of the fourPlasmodiumspecies that cause human malaria,Plasmodium fal-ciparumis responsible for the most severe form of the disease and this par-asite is developing resistance to the major antimalarial drugs. Therefore, in order to control malaria it is necessary to identify new drug targets. | ỊFEBS Journal MINIREVIEW Helicases - feasible antimalarial drug target for Plasmodium falciparum Renu Tuteja Malaria Group InternationalCentre for Genetic Engineering and Biotechnology New Delhi India Keywords DEAD-box DNA unwinding DNA-dependent ATPase DNA-interacting compounds drug target helicase inhibitors malaria parasite molecular motor Plasmodium falciparum Correspondence R. Tuteja Malaria Group International Centre for Genetic Engineering and Biotechnology Aruna Asaf Ali Marg New Delhi-110067 India Fax 91 11 2674 2316 Tel 91 11 2674 1358 E-mail renu@ Of the four Plasmodium species that cause human malaria Plasmodium falciparum is responsible for the most severe form of the disease and this parasite is developing resistance to the major antimalarial drugs. Therefore in order to control malaria it is necessary to identify new drug targets. One feasible target might be helicases which are important unwinding enzymes and required for almost all the nucleic acid metabolism in the malaria parasite. Received 23 April2007 revised 23 May 2007 accepted 19 July 2007 doi The universal presence of helicases in eukaryotes and prokaryotes including parasites reflects their fundamental importance in DNA and RNA metabolic processes and the maintenance of genomic stability 1-4 . The emerging evidence demonstrates that helicases are indispensable enzymes because a growing number of human genetic disorders are attributed to mutations in helicase genes 1-4 . Helicases act on double-stranded nucleic acid substrate and thus can be designated DNA-DNA RNA-DNA or RNA-RNA helicases depending on the composition of the substrate. They are also known as motor proteins because to unwind the duplexes they require energy which is provided by their intrinsic nucleic acid-dependent ATPase activity. These enzymes act as necessary molecular tools for cellular machinery and significantly contribute to normal cellular metabolism. In general helicases