Plasmodium cynomolgi DEAD-box
DNA helicase 45 (PcDDH45) is an
ATP-dependent
DNA-unwinding
enzyme with intrinsic
DNA-dependent ATPase activity and is highly homologous to
eIF-4A. In this study, we have further characterized and tested the effect of various
DNA-interacting compounds on the
DNA-unwinding activity of PcDDH45. The results show that PcDDH45 translocates in the 3' to 5' direction along the bound strand, a replication fork-like structure of the substrate stimulates its
DNA-unwinding activity, and it failed to unwind blunt-ended duplex
DNA. Of various compounds tested, only
cisplatin, 4',6'-diamidino-2-phenylindole,
daunorubicin, and
nogalamycin were inhibitory to the unwinding activity of PcDDH45 with apparent IC(50) values of 1.0, 4.0, 7.5, and 1.7 microM, respectively. These results suggest that the interaction of these compounds with duplex
DNA generate a complex that probably impedes the translocation of PcDDH45, resulting in inhibition of unwinding activity. This study is one of the first to demonstrate the effect of various
DNA-binding compounds on a
malaria parasite
DNA helicase and should make an important contribution to our better understanding of the
nucleic acid transactions in the parasite.