A Plasmodium multi-domain protein possesses multiple inositol phosphate kinase activities.

The synchronization of intraerythrocytic maturation of Plasmodium parasites is an important factor in the malaria infection process. Synchronization is mediated by inositol phosphate (InsPx)-induced Ca2+-release from internal stores. To further investigate the InsPx metabolism in these parasites a Plasmodium protein possessing inositol phosphate kinase (IPK) activity was recombinantly expressed, purified and enzymatically characterized for the first time. Its main activity is the conversion of the Ca2+-releasing second messenger Ins(1,4,5)P3 to Ins(1,3,4,5)P4, an important factor in chromatin remodeling and also in Ca2+-release. This protein possesses several additional IPK activities pointing to a potential role as inositol phosphate multikinase. Interestingly, we have also identified three putative subdomains of histone deacetylase in this protein possibly linking InsPx- and acetylation-mediated transcription regulation. Furthermore, we examined the inhibitory potential of >40 polyphenolic substances against its kinase activity. Because of the important role of InsPx-induced Ca2+-release in the development of Plasmodium parasites, IPKs are interesting targets for novel antimalarial approaches.