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Cited by 9Phytase and its ApplicationsCalcium signaling and nucleotide metabolismProtein Kinase Regulation and GTPase Signaling

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A small signaling domain controls PPIP5K phosphatase activity in phosphate homeostasis

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Raia, Pierre, Lee, Kitaik, Bartsch, Simon M., Rico-Resendiz, Felix, Portugal-Calisto, Daniela, Vadas, Oscar, Panse, Vikram Govind, Fiedler, Dorothea, Hothorn, Michael·2025·Nature Communications
DOI 10.1038/s41467-025-56937-0PMC PMC11836120

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Abstract

Inositol pyrophosphates (PP-InsPs) are eukaryotic nutrient messengers. The N-terminal kinase domain of diphosphoinositol pentakisphosphate kinase (PPIP5K) generates the messenger 1,5-InsP 8 , the C-terminal phosphatase domain catalyzes PP-InsP breakdown. The balance between kinase and phosphatase activities regulates 1,5-InsP 8 levels. Here, we present crystal structures of the apo and substrate-bound PPIP5K phosphatase domain from S. cerevisiae (ScVip1 PD ). ScVip1 PD is a phytase-like inositol 1-pyrophosphate histidine phosphatase with two conserved catalytic motifs. The enzyme has a strong preference for 1,5-InsP 8 and is inhibited by inorganic phosphate. It contains an α-helical insertion domain stabilized by a structural Zn 2+ binding site, and a unique GAF domain that channels the substrate to the active site. Mutations that alter the active site, restrict the movement of the GAF domain, or change the substrate channel’s charge inhibit the enzyme activity in vitro, and Arabidopsis VIH2 in planta . Our work reveals the structure, enzymatic mechanism and regulation of eukaryotic PPIP5K phosphatases.

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  1. Shears, S. B. Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling. J. Cell. Physiol. 233, 1897–1912 (2018). · DOI
  2. Gu, C., Li, X., Zong, G., Wang, H. & Shears, S. B. IP8: a quantitatively minor inositol pyrophosphate signaling molecule that punches above its weight. Adv. Biol. Regul. 91, 101002 (2024). · DOI
  3. Nguyen Trung, M., Furkert, D. & Fiedler, D. Versatile signaling mechanisms of inositol pyrophosphates. Curr. Opin. Chem. Biol. 70, 102177 (2022). · DOI
  4. Wild, R. et al. Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science 352, 986–990 (2016). · DOI
  5. Chabert, V. et al. Inositol pyrophosphate dynamics reveals control of the yeast phosphate starvation program through 1,5-IP8 and the SPX domain of Pho81. Elife 12, RP87956 (2023). · DOI
  6. Guan, Z. et al. The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex. Nat. Commun. 14, 718 (2023). · DOI
  7. Cordeiro, C. D., Saiardi, A. & Docampo, R. The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes. Mol. Microbiol. 106, 319–333 (2017). · DOI
  8. Couso, I. et al. Synergism between inositol polyphosphates and TOR kinase signaling in nutrient sensing, growth control, and lipid metabolism in Chlamydomonas. Plant Cell 28, 2026–2042 (2016). · DOI
  9. Stevenson-Paulik, J., Bastidas, R. J., Chiou, S.-T., Frye, R. A. & York, J. D. Generation of phytate-free seeds in Arabidopsis through disruption of inositol polyphosphate kinases. Proc. Natl Acad. Sci. USA 102, 12612–12617 (2005). · DOI
  10. Zhu, J. et al. Two bifunctional inositol pyrophosphate kinases/phosphatases control plant phosphate homeostasis. eLife 8, e43582 (2019). · DOI
  11. Dong, J. et al. Inositol pyrophosphate InsP8 acts as an intracellular phosphate signal in Arabidopsis. Mol. Plant https://doi.org/10.1016/j.molp.2019.08.002 (2019). · DOI
  12. Ried, M. K. et al. Inositol pyrophosphates promote the interaction of SPX domains with the coiled-coil motif of PHR transcription factors to regulate plant phosphate homeostasis. Nat. Commun. 12, 384 (2021). · DOI
  13. Riemer, E. et al. ITPK1 is an InsP6/ADP phosphotransferase that controls phosphate signaling in Arabidopsis. Mol. Plant 14, 1864–1880 (2021). · DOI
  14. Zhou, J. et al. Mechanism of phosphate sensing and signaling revealed by rice SPX1-PHR2 complex structure. Nat. Commun. 12, 7040 (2021). · DOI
  15. Guan, Z. et al. Mechanistic insights into the regulation of plant phosphate homeostasis by the rice SPX2—PHR2 complex. Nat. Commun. 13, 1581 (2022). · DOI
  16. Gu, C. et al. The significance of the bifunctional kinase/phosphatase activities of diphosphoinositol pentakisphosphate kinases (PPIP5Ks) for coupling inositol pyrophosphate cell signaling to cellular phosphate homeostasis. J. Biol. Chem. 292, 4544–4555 (2017). · DOI
  17. Li, X. et al. Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. PNAS 117, 3568–3574 (2020). · DOI
  18. Wang, Z. et al. Rapid stimulation of cellular Pi uptake by the inositol pyrophosphate InsP 8 induced by its photothermal release from lipid nanocarriers using a near infra-red light-emitting diode. Chem. Sci. 11, 10265–10278 (2020). · DOI
  19. Li, X. et al. Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. Cell Rep. 43, 114316 (2024). · DOI
  20. Saiardi, A., Erdjument-Bromage, H., Snowman, A. M., Tempst, P. & Snyder, S. H. Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr. Biol. 9, 1323–1326 (1999). · DOI · Paper page
  21. Dubois, E. et al. In Saccharomyces cerevisiae, the inositol polyphosphate kinase activity of Kcs1p is required for resistance to salt stress, cell wall integrity, and vacuolar morphogenesis. J. Biol. Chem. 277, 23755–23763 (2002). · DOI
  22. Laha, D. et al. Arabidopsis ITPK1 and ITPK2 have an evolutionarily conserved phytic acid kinase activity. ACS Chem. Biol. 14, 2127–2133 (2019). · DOI
  23. Fridy, P. C., Otto, J. C., Dollins, D. E. & York, J. D. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J. Biol. Chem. 282, 30754–30762 (2007). · DOI
  24. Mulugu, S. et al. A conserved family of enzymes that phosphorylate inositol hexakisphosphate. Science 316, 106–109 (2007). · DOI
  25. Dollins, D. E. et al. Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling. Proc. Natl Acad. Sci. USA 117, 9356–9364 (2020). · DOI
  26. Gokhale, N. A., Zaremba, A. & Shears, S. B. Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain. Biochem. J. 434, 415–426 (2011). · DOI
  27. Wang, H., Falck, J. R., Hall, T. M. T. & Shears, S. B. Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding. Nat. Chem. Biol. 8, 111–116 (2012). · DOI
  28. Weaver, J. D., Wang, H. & Shears, S. B. The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment. Biosci. Rep. 33, e00022 (2013). · DOI
  29. Nair, V. S. et al. Inositol pyrophosphate synthesis by diphosphoinositol pentakisphosphate kinase-1 is regulated by phosphatidylinositol(4,5)bisphosphate. Biosci. Rep. 38, BSR20171549 (2018). · DOI
  30. Desfougères, Y. et al. The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis. Adv. Biol. Regul. 83, 100835 (2022). · DOI
  31. Desai, M. et al. Two inositol hexakisphosphate kinases drive inositol pyrophosphate synthesis in plants. Plant J. 80, 642–653 (2014). · DOI
  32. Laha, D. et al. VIH2 regulates the synthesis of inositol pyrophosphate InsP8 and jasmonate-dependent defenses in Arabidopsis. Plant Cell 27, 1082–1097 (2015). · DOI
  33. Shukla, A. et al. Wheat inositol pyrophosphate kinase TaVIH2-3B modulates cell-wall composition and drought tolerance in Arabidopsis. BMC Biol. 19, 261 (2021). · DOI
  34. Laurent, F. et al. Inositol pyrophosphate catabolism by three families of phosphatases regulates plant growth and development. PLoS Genet 20, e1011468 (2024). · DOI
  35. Pascual-Ortiz, M. et al. Asp1 bifunctional activity modulates spindle function via controlling cellular inositol pyrophosphate levels in Schizosaccharomyces pombe. Mol. Cell. Biol. 38, e00047-18 (2018). · DOI
  36. Gu, C. et al. KO of 5-InsP7 kinase activity transforms the HCT116 colon cancer cell line into a hypermetabolic, growth-inhibited phenotype. Proc. Natl Acad. Sci. USA 114, 11968–11973 (2017). · DOI
  37. Yousaf, R. et al. Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse. PLoS Genet. 14, e1007297 (2018). · DOI
  38. Gu, C. et al. Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase/phosphatase, controls proliferation of the HCT116 tumor cell line. Proc. Natl Acad. Sci. USA 118, e2020187118 (2021). · DOI
  39. Gulabani, H. et al. Arabidopsis inositol polyphosphate kinases IPK1 and ITPK1 modulate crosstalk between SA-dependent immunity and phosphate-starvation responses. Plant Cell Rep. 41, 347–363 (2022). · DOI
  40. Benjamin, B. et al. Activities and structure-function analysis of fission yeast inositol pyrophosphate (IPP) kinase-pyrophosphatase Asp1 and its impact on regulation of pho1 gene expression. mBio 13, e01034-22 (2022). · DOI
  41. Pöhlmann, J. et al. The Vip1 inositol polyphosphate kinase family regulates polarized growth and modulates the microtubule cytoskeleton in fungi. PLoS Genet. 10, e1004586 (2014). · DOI
  42. Wang, H. et al. Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S]2+ cluster which inhibits inositol pyrophosphate 1-phosphatase activity. Biochemistry 54, 6462–6474 (2015). · DOI
  43. Gu, C., Wilson, M. S. C., Jessen, H. J., Saiardi, A. & Shears, S. B. Inositol pyrophosphate profiling of two HCT116 cell lines uncovers variation in InsP8 levels. PLoS ONE 11, e0165286 (2016). · DOI
  44. Qiu, D. et al. Analysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry. Nat. Commun. 11, 6035 (2020). · DOI
  45. Wang, H. et al. Synthetic inositol phosphate analogs reveal that PPIP5K2 has a surface-mounted substrate capture site that is a target for drug discovery. Chem. Biol. 21, 689–699 (2014). · DOI
  46. Benjamin, B. et al. Structures of fission yeast inositol pyrophosphate kinase Asp1 in ligand-free, substrate-bound, and product-bound states. mBio 13, e03087–22 (2022). · DOI
  47. Rigden, D. J. The histidine phosphatase superfamily: structure and function. Biochem. J. 409, 333–348 (2008). · DOI
  48. Ostanin, K. et al. Overexpression, site-directed mutagenesis, and mechanism of Escherichia coli acid phosphatase. J. Biol. Chem. 267, 22830–22836 (1992). · DOI
  49. Scheffzek, K. & Welti, S. Pleckstrin homology (PH) like domains—versatile modules in protein–protein interaction platforms. FEBS Lett. 586, 2662–2673 (2012). · DOI
  50. Holm, L. & Rosenström, P. Dali server: conservation mapping in 3D. Nucl. Acids Res. 38, W545–W549 (2010). · DOI · Paper page
  51. Aravind, L. & Ponting, C. P. The GAF domain: an evolutionary link between diverse phototransducing proteins. Trends Biochem Sci. 22, 458–459 (1997). · DOI
  52. Ponting, C. P. & Aravind, L. PAS: a multifunctional domain family comes to light. Curr. Biol. 7, R674–R677 (1997). · DOI
  53. Ho, Y. J., Burden, L. M. & Hurley, J. H. Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. EMBO J. 19, 5288–5299 (2000). · DOI
  54. Henry, J. T. & Crosson, S. Ligand-binding PAS domains in a genomic, cellular, and structural context. Annu. Rev. Microbiol. 65, 261–286 (2011). · DOI
  55. Milburn, C. C. et al. Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change. Biochem. J. 375, 531–538 (2003). · DOI
  56. Wang, Q. et al. Autoinhibition of Bruton’s tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate. Elife 4, e06074 (2015). · DOI
  57. Lim, D., Golovan, S., Forsberg, C. W. & Jia, Z. Crystal structures of Escherichia coli phytase and its complex with phytate. Nat. Struct. Biol. 7, 108–113 (2000). · DOI
  58. Ostanin, K. & Van Etten, R. L. Asp304 of Escherichia coli acid phosphatase is involved in leaving group protonation. J. Biol. Chem. 268, 20778–20784 (1993). · DOI
  59. Auesukaree, C. et al. Intracellular phosphate serves as a signal for the regulation of the PHO pathway in Saccharomyces cerevisiae. J. Biol. Chem. 279, 17289–17294 (2004). · DOI
  60. Acquistapace, I. M. et al. Insights to the structural basis for the stereospecificity of the Escherichia coli Phytase, AppA. IJMS 23, 6346 (2022). · DOI
  61. Stentz, R. et al. A bacterial homolog of a eukaryotic inositol phosphate signaling enzyme mediates cross-kingdom dialog in the mammalian gut. Cell Rep. 6, 646–656 (2014). · DOI
  62. Pan, X. et al. A robust toolkit for functional profiling of the yeast genome. Mol. Cell 16, 487–496 (2004). · DOI
  63. Masinas, M. P. D., Usaj, M. M., Usaj, M., Boone, C. & Andrews, B. J. TheCellVision.org: a database for visualizing and mining high-content cell imaging projects. G3 10, 3969–3976 (2020). · DOI
  64. Schwartz, K., Richards, K. & Botstein, D. BIM1 encodes a microtubule-binding protein in yeast. Mol. Biol. Cell 8, 2677–2691 (1997). · DOI
  65. Manatschal, C. et al. Molecular basis of Kar9-Bim1 complex function during mating and spindle positioning. Mol. Biol. Cell 27, 3729–3745 (2016). · DOI
  66. An, Y., Jessen, H. J., Wang, H., Shears, S. B. & Kireev, D. Dynamics of substrate processing by PPIP5K2, a versatile catalytic machine. Structure 27, 1022–1028.e2 (2019). · DOI
  67. Sanchez, A. M., Schwer, B., Jork, N., Jessen, H. J. & Shuman, S. Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase. mBio 14, e02056–23 (2023). · DOI
  68. Ghosh, S. et al. Activities and genetic interactions of fission yeast Aps1, a Nudix-type inositol pyrophosphatase and inorganic polyphosphatase. mBio 15, e0108424 (2024). · DOI
  69. Garg, A., Shuman, S. & Schwer, B. A genetic screen for suppressors of hyper-repression of the fission yeast PHO regulon by Pol2 CTD mutation T4A implicates inositol 1-pyrophosphates as agonists of precocious lncRNA transcription termination. Nucleic Acids Res. 48, 10739–10752 (2020). · DOI
  70. Wang, H., Gu, C., Rolfes, R. J., Jessen, H. J. & Shears, S. B. Structural and biochemical characterization of Siw14: a protein-tyrosine phosphatase fold that metabolizes inositol pyrophosphates. J. Biol. Chem. 293, 6905–6914 (2018). · DOI
  71. Lee, Y.-H., Li, Y., Uyeda, K. & Hasemann, C. A. Tissue-specific structure/function differentiation of the liver isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. J. Biol. Chem. 278, 523–530 (2003). · DOI
  72. Machkalyan, G., Trieu, P., Pétrin, D., Hébert, T. E. & Miller, G. J. PPIP5K1 interacts with the exocyst complex through a C-terminal intrinsically disordered domain and regulates cell motility. Cell. Signal. 28, 401–411 (2016). · DOI
  73. Hothorn, M., Dabi, T. & Chory, J. Structural basis for cytokinin recognition by Arabidopsis thaliana histidine kinase 4. Nat. Chem. Biol. 7, 766–768 (2011). · DOI
  74. Hashimoto, Y., Zhang, S. & Blissard, G. W. Ao38, a new cell line from eggs of the black witch moth, Ascalapha odorata (Lepidoptera: Noctuidae), is permissive for AcMNPV infection and produces high levels of recombinant proteins. BMC Biotechnol. 10, 50 (2010). · DOI
  75. Malakhov, M. P. et al. SUMO fusions and SUMO-specific protease for efficient expression and purification of proteins. J. Struct. Funct. Genom. 5, 75–86 (2004). · DOI
  76. Gorrec, F. The MORPHEUS protein crystallization screen. J. Appl Crystallogr 42, 1035–1042 (2009). · DOI
  77. Kabsch, W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry land cell constants. J. Appl. Crystallogr. 26, 795–800 (1993). · DOI
  78. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007). · DOI · Paper page
  79. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Cryst. D. 60, 2126–2132 (2004). · DOI · Paper page
  80. Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Cryst. D. 68, 352–367 (2012). · DOI · Paper page
  81. Read, R. J. & McCoy, A. J. Using SAD data in Phaser. Acta Crystallogr D. Biol. Crystallogr 67, 338–344 (2011). · DOI
  82. Terwilliger, T. C. SOLVE and RESOLVE: automated structure solution and density modification. Meth. Enzymol. 374, 22–37 (2003). · DOI
  83. Lebedev, A. A. & Isupov, M. N. Space-group and origin ambiguity in macromolecular structures with pseudo-symmetry and its treatment with the program Zanuda. Acta Cryst. D. 70, 2430–2443 (2014). · DOI
  84. Ban, N. et al. Placement of protein and RNA structures into a 5 A-resolution map of the 50S ribosomal subunit. Nature 400, 841–847 (1999). · DOI
  85. Wittmann, J. G. & Rudolph, M. G. Pseudo-merohedral twinning in monoclinic crystals of human orotidine-5’-monophosphate decarboxylase. Acta Crystallogr D. Biol. Crystallogr 63, 744–749 (2007). · DOI
  86. Davis, I. W. et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35, W375–W383 (2007). · DOI
  87. Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput Chem. 25, 1605–1612 (2004). · DOI
  88. Harmel, R. K. et al. Harnessing 13C-labeled myo-inositol to interrogate inositol phosphate messengers by NMR. Chem. Sci. 10, 5267–5274 (2019). · DOI
  89. Ames, B. Assay of inorganic phosphate, total phosphate and phosphatases. Methods Enzymol. 8, 115–118 (1966). · DOI
  90. Baykov, A. A., Evtushenko, O. A. & Avaeva, S. M. A malachite green procedure for orthophosphate determination and its use in alkaline phosphatase-based enzyme immunoassay. Anal. Biochem. 171, 266–270 (1988). · DOI
  91. Longtine, M. S. et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14, 953–961 (1998). · DOI
  92. Clough, S. J. & Bent, A. F. Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. Plant J. 16, 735–743 (1998). · DOI
  93. Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012). · DOI · Paper page
  94. Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017). · DOI · Paper page
  95. Wang, H. et al. Autoregulation of class II alpha PI3K activity by its lipid-binding PX-C2 domain module. Mol. Cell 71, 343–351.e4 (2018). · DOI
  96. Hostachy, S. et al. Dissecting the activation of insulin degrading enzyme by inositol pyrophosphates and their bisphosphonate analogs. Chem. Sci. 12, 10696–10702 (2021). · DOI
  97. Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2022). · DOI · Paper page
  98. Ortlund, E., LaCount, M. W. & Lebioda, L. Crystal structures of human prostatic acid phosphatase in complex with a phosphate ion and α-benzylaminobenzylphosphonic acid update the mechanistic picture and offer new insights into inhibitor design. Biochemistry 42, 383–389 (2003). · DOI
  99. Hamada, K. et al. Crystal structure of the protein histidine phosphatase SixA in the multistep His‐Asp phosphorelay. Genes Cells 10, 1–11 (2005). · DOI
  100. Landau, M. et al. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 33, W299–W302 (2005). · DOI
  101. Dunnett, C. W. A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50, 1096–1121 (1955). · DOI

Metadata

Authors
Raia, P., Lee, K., Bartsch, S. M., Rico-Resendiz, F., Portugal-Calisto, D., Vadas, O., Panse, V. G., Fiedler, D., & Hothorn, M.
Affiliations
  • University of Geneva (CH)
  • Humboldt-Universität zu Berlin (DE)
  • University of Zurich (CH)
Corresponding author
Hothorn, Michael
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-02-19
Volume
16
Issue
1
Pages
1753-1753
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-56937-0
PMC
PMC11836120
OpenAlex
W4407682565
Cited by
9
References
105
Citations by year
2026: 5 · 2025: 4
FWCI
4.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII5_209412)
  • Howard Hughes Medical Institute (55008733)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytase and its Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
phosphatase domain, inositol pyrophosphates, phosphate homeostasis, GAF domain, zinc binding site, substrate channel, enzyme crystal structure, enzyme mechanism, signaling domains
MeSH terms
Protein Domains, Homeostasis, Inositol Phosphates, Models, Molecular, Mutation, Phosphates, Phosphoric Monoester Hydrolases, Saccharomyces cerevisiae, Substrate Specificity, Signal Transduction, Arabidopsis, Phosphotransferases (Phosphate Group Acceptor), Crystallography, X-Ray, Catalytic Domain, Arabidopsis Proteins, Saccharomyces cerevisiae Proteins

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