title: A novel Entamoeba histolytica inositol phosphate kinase catalyzes the formation of 5PP-Ins(1,2,3,4,6)P(5).
abstract: The parasitic protozoan Entamoeba histolytica is able to invade human tissues by secreting proteolytic enzymes. This secretion is regulated by inositol phosphate-mediated Ca(2+) release from internal stores. To further investigate the inositol phosphate metabolism of Entamoeba histolytica four putative inositol phosphate kinase genes (ehipk1-4) were identified and their expression analyzed by real-time quantitative PCR using RNA of trophozoites. Furthermore inositol phosphate kinase EhIPK1 was recombinantly expressed, purified and enzymatically characterized. Its main activity is the conversion of InsP(6) to 5PP-Ins(1,2,3,4,6)P(5), one of the main inositol phosphates found in Entamoeba histolytica. Remarkably, EhIPK1 possesses several additional enzymatic activities, e.g. the phosphorylation of the Ca(2+)-releasing second messenger Ins(1,4,5)P(3).We were able to identify several compounds with inhibitory potential against EhIPK1. Because of the important role of inositol phosphates in the invasion of human tissues by Entamoeba histolytica, inositol phosphate metabolizing enzymes are interesting targets for novel therapeutic approaches.
authors: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors: Benjamin
authors: B
authors: Löser
authors: Marcus M
authors: MM
authors: Nalaskowski
authors: Werner
authors: W
authors: Fanick
authors: Hongying
authors: H
authors: Lin
authors: Egbert
authors: E
authors: Tannich
authors: Georg W
authors: GW
authors: Mayr
mesh_terms: D000595:Amino Acid Sequence; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D007295:Inositol Phosphates / Q000378:metabolism*; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D011994:Recombinant Proteins; C519006:inositol 1,2,3,4,6-pentaphospate 5-pyrophosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase