A novel 6-pyrophosphorylating IP6 kinase (IP6-6K) discovered in the protozoon Trichomonas vaginalis

[Display omitted] •The parasitic protozoon T. vaginalis is the pathogen of trichomoniasis.•Inositol phosphates are involved in adaption to oxygen exposure during change of host.•Six inositol phosphate kinase genes were identified in the T. vaginalis genome by us.•The major activity of TvIP6K1 is the conversion of InsP6 to 6PP-InsP5.•TvIP6K1 also phosphorylates the 3-OH group of Ins(1,2,4,5)P4 and Ins(1,2,4,5,6)P5. The parasitic protozoon Trichomonas vaginalis is the pathogen of trichomoniasis, the most common non-viral, sexually transmitted disease in humans. Inositol phosphates function in the pathomechanisms of a number of human pathogenic protozoa. Recent findings point to a role of inositol phosphates in T. vaginalis’ adaption to oxygen exposure during change of host. Six inositol phosphate kinase genes (tvip6k1-4, tvipk1-2) were identified in the T. vaginalis genome by us all coding for proteins containing canonical sequence motifs of the major group of animal inositol phosphate kinases (PDKG, SSLL, DFG/A). When characterizing the purified protein product of tvip6k1, we discovered that the major activity of the highly active enzyme (˜2 μmol/min/mg) is a conversion of InsP6 to 6PP-InsP5 and not 5PP-InsP5 as by animal isoforms. Thus TvIP6K1 is a novel IP6-6K. The enzyme also converts Ins(1,3,4,5,6)P5 to products pyrophosphorylated both at 6- and 4-phosphate still having a free 5-hydroxyl. In addition, the enzyme has a minor selectivity to phosphorylate the 3-OH in Ins(1,2,4,5)P4 and Ins(1,2,4,5,6)P5. To present knowledge this novel enzyme is restricted to protozoa. Since its structure is predicted to be distinctly different from animal IP6K (IP6-5K) forms, TvIP6-6K may become a promising target to search for novel trichomoniasis specific drugs.