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

作者：Stritzke Carina; Nalaskowski Marcus M^*; Fanick Werner; Lin Hongying; Mayr Georg W

来源：Molecular and Biochemical Parasitology, 2012, 186(2): 134-138.

DOI：10.1016/j.molbiopara.2012.10.005

• Plasmodium knowlesi
• Inositol phosphates
• Inositol phosphate kinase
• Histone deacetylase
• Intraerythrocytic development
• Chromatin remodeling

The synchronization of intraerythrocytic maturation of Plasmodium parasites is an important factor in the malaria infection process. Synchronization is mediated by inositol phosphate (InsP(x))-induced Ca2+-release from internal stores. To further investigate the InsP(x) 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)P-3 to Ins(1,3,4,5)P-4, 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 InsP(x)- 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 InsP(x)-induced Ca2+-release in the development of Plasmodium parasites, IPKs are interesting targets for novel antimalarial approaches.

• 出版日期2012-12