A novel 6-pyrophosphorylating IP6 kinase (IP6-6K) discovered in the protozoon Trichomonas vaginalis
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A novel 6-pyrophosphorylating IP6 kinase (IP6-6K) discovered in the protozoon Trichomonas vaginalis. / Wundenberg, Torsten; Nalaskowski, Marcus M; Löser, Benjamin; Fanick, Werner; Hackl, Thomas; Fürnkranz, Ursula; Rehbach, Christoph; Lin, Hongying; Mayr, Georg W.
In: MOL BIOCHEM PARASIT, Vol. 227, 01.2019, p. 53-63.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -