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

TY - JOUR

T1 - A novel 6-pyrophosphorylating IP6 kinase (IP6-6K) discovered in the protozoon Trichomonas vaginalis

AU - Wundenberg, Torsten

AU - Nalaskowski, Marcus M

AU - Löser, Benjamin

AU - Fanick, Werner

AU - Hackl, Thomas

AU - Fürnkranz, Ursula

AU - Rehbach, Christoph

AU - Lin, Hongying

AU - Mayr, Georg W

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Humans

KW - Inositol Phosphates

KW - Kinetics

KW - Multigene Family

KW - Phosphorylation

KW - Protein Kinases

KW - Protozoan Proteins

KW - Sequence Alignment

KW - Trichomonas vaginalis

KW - Journal Article

U2 - 10.1016/j.molbiopara.2018.12.004

DO - 10.1016/j.molbiopara.2018.12.004

M3 - SCORING: Journal article

C2 - 30593849

VL - 227

SP - 53

EP - 63

JO - MOL BIOCHEM PARASIT

JF - MOL BIOCHEM PARASIT

SN - 0166-6851

ER -