کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2829808 | 1163302 | 2012 | 5 صفحه PDF | دانلود رایگان |
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.
For the first time a Plasmodium inositol phosphate kinase was identified. It metabolizes Ins(1,4,5)P3, an inositol phosphate involved in intraerythrocytic maturation of these parasites.Figure optionsDownload high-quality image (92 K)Download as PowerPoint slideHighlights
► For the first time a Plasmodium inositol phosphate kinase was identified.
► A recombinant protein fragment was expressed and enzymatically characterized.
► Its main substrate Ins(1,4,5)P3 is involved in intraerythrocytic maturation.
► It also metabolizes several additional inositol phosphate isomers.
► Three putative histone deacetylase subdomains were identified in the protein.
Journal: Molecular and Biochemical Parasitology - Volume 186, Issue 2, December 2012, Pages 134–138