title: A Plasmodium multi-domain protein possesses multiple inositol phosphate kinase activities.
abstract: 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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-release in the development of Plasmodium parasites, IPKs are interesting targets for novel antimalarial approaches.
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Stritzke
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Nalaskowski
authors.forename: Werner
authors.initials: W
authors.lastname: Fanick
authors.forename: Hongying
authors.initials: H
authors.lastname: Lin
authors.forename: Georg W
authors.initials: GW
authors.lastname: Mayr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010961:Plasmodium / Q000235:genetics / Q000378:metabolism*; D059808:Polyphenols / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D004791:Enzyme Inhibitors; D059808:Polyphenols; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase