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

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 (P-D-K-G, SSLL, DFG/A). When characterizing the purified protein product of tvip6k-1, we discovered that the major activity of the highly active enzyme (˜2 µmol/min/mg) is a conversion of InsP6 to 6-PP-InsP5 and not 5-PP-InsP5 as by animal isoforms. Thus TvIP6 K1 is a novel IP6-6 K. 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 IP6 K (IP6-5 K) forms, TvIP6-6 K may become a promising target to search for novel trichomoniasis specific drugs.