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Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding.

Wang H, Falck JR, Hall TM, Shears SB
Nat Chem Biol 8 111-6 (2011)
Related entries: 3t7a, 3t99, 3t9a, 3t9b, 3t9c, 3t9d, 3t9e, 3t9f

Cited: 78 times
EuropePMC logo PMID: 22119861

Abstract

Inositol pyrophosphates (such as IP7 and IP8) are multifunctional signaling molecules that regulate diverse cellular activities. Inositol pyrophosphates have 'high-energy' phosphoanhydride bonds, so their enzymatic synthesis requires that a substantial energy barrier to the transition state be overcome. Additionally, inositol pyrophosphate kinases can show stringent ligand specificity, despite the need to accommodate the steric bulk and intense electronegativity of nature's most concentrated three-dimensional array of phosphate groups. Here we examine how these catalytic challenges are met by describing the structure and reaction cycle of an inositol pyrophosphate kinase at the atomic level. We obtained crystal structures of the kinase domain of human PPIP5K2 complexed with nucleotide cofactors and either substrates, product or a MgF(3)(-) transition-state mimic. We describe the enzyme's conformational dynamics, its unprecedented topological presentation of nucleotide and inositol phosphate, and the charge balance that facilitates partly associative in-line phosphoryl transfer.

Reviews - 3t54 mentioned but not cited (1)

  1. The enzymes of human diphosphoinositol polyphosphate metabolism. Thomas MP, Potter BV. FEBS J 281 14-33 (2014)

Articles - 3t54 mentioned but not cited (2)

  1. Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding. Wang H, Falck JR, Hall TM, Shears SB. Nat Chem Biol 8 111-116 (2011)
  2. A High-Throughput Screening-Compatible Strategy for the Identification of Inositol Pyrophosphate Kinase Inhibitors. Baughman BM, Wang H, An Y, Kireev D, Stashko MA, Jessen HJ, Pearce KH, Frye SV, Shears SB. PLoS One 11 e0164378 (2016)


Reviews citing this publication (21)

  1. Inositol pyrophosphates: why so many phosphates? Shears SB. Adv Biol Regul 57 203-216 (2015)
  2. Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling. Shears SB. J Cell Physiol 233 1897-1912 (2018)
  3. The emerging roles of inositol pyrophosphates in eukaryotic cell physiology. Thota SG, Bhandari R. J Biosci 40 593-605 (2015)
  4. Identity and functions of inorganic and inositol polyphosphates in plants. Lorenzo-Orts L, Couto D, Hothorn M. New Phytol 225 637-652 (2020)
  5. Biosynthesis and possible functions of inositol pyrophosphates in plants. Williams SP, Gillaspy GE, Perera IY. Front Plant Sci 6 67 (2015)
  6. Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals. Lee S, Kim MG, Ahn H, Kim S. Molecules 25 E2208 (2020)
  7. A two-way switch for inositol pyrophosphate signaling: Evolutionary history and biological significance of a unique, bifunctional kinase/phosphatase. Randall TA, Gu C, Li X, Wang H, Shears SB. Adv Biol Regul 75 100674 (2020)
  8. Phosphate Homeostasis - A Vital Metabolic Equilibrium Maintained Through the INPHORS Signaling Pathway. Austin S, Mayer A. Front Microbiol 11 1367 (2020)
  9. Inositol phosphate kinases: Expanding the biological significance of the universal core of the protein kinase fold. Shears SB, Wang H. Adv Biol Regul 71 118-127 (2019)
  10. Chemical tools for interrogating inositol pyrophosphate structure and function. Brown NW, Marmelstein AM, Fiedler D. Chem Soc Rev 45 6311-6326 (2016)
  11. Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases. Mukherjee S, Haubner J, Chakraborty A. Molecules 25 E1403 (2020)
  12. Structural insight into inositol pyrophosphate turnover. Shears SB, Weaver JD, Wang H. Adv Biol Regul 53 19-27 (2013)
  13. Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules. Shah A, Ganguli S, Sen J, Bhandari R. J Indian Inst Sci 97 23-40 (2017)
  14. Importance of Radioactive Labelling to Elucidate Inositol Polyphosphate Signalling. Wilson MSC, Saiardi A. Top Curr Chem (Cham) 375 14 (2017)
  15. Metabolism and Functions of Inositol Pyrophosphates: Insights Gained from the Application of Synthetic Analogues. Shears SB, Wang H. Molecules 25 E4515 (2020)
  16. Towards pharmacological intervention in inositol pyrophosphate signalling. Shears SB. Biochem Soc Trans 44 191-196 (2016)
  17. Inositol Pyrophosphate Pathways and Mechanisms: What Can We Learn from Plants? Cridland C, Gillaspy G. Molecules 25 E2789 (2020)
  18. Regulation of plant biotic interactions and abiotic stress responses by inositol polyphosphates. Riemer E, Pullagurla NJ, Yadav R, Rana P, Jessen HJ, Kamleitner M, Schaaf G, Laha D. Front Plant Sci 13 944515 (2022)
  19. Reflections on biocatalysis involving phosphorus. Blackburn GM, Bowler MW, Jin Y, Waltho JP. Biochemistry (Mosc) 77 1083-1096 (2012)
  20. Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsP5 and InsP8 in mammalian cells. Qi J, Shi L, Zhu L, Chen Y, Zhu H, Cheng W, Chen AF, Fu C. J Cardiovasc Transl Res (2023)
  21. Plant phosphate nutrition: sensing the stress. Satheesh V, Tahir A, Li J, Lei M. Stress Biol 2 16 (2022)

Articles citing this publication (54)

  1. VIH2 Regulates the Synthesis of Inositol Pyrophosphate InsP8 and Jasmonate-Dependent Defenses in Arabidopsis. Laha D, Johnen P, Azevedo C, Dynowski M, Weiß M, Capolicchio S, Mao H, Iven T, Steenbergen M, Freyer M, Gaugler P, de Campos MK, Zheng N, Feussner I, Jessen HJ, Van Wees SC, Saiardi A, Schaaf G. Plant Cell 27 1082-1097 (2015)
  2. Two bifunctional inositol pyrophosphate kinases/phosphatases control plant phosphate homeostasis. Zhu J, Lau K, Puschmann R, Harmel RK, Zhang Y, Pries V, Gaugler P, Broger L, Dutta AK, Jessen HJ, Schaaf G, Fernie AR, Hothorn LA, Fiedler D, Hothorn M. Elife 8 e43582 (2019)
  3. Human genome-wide RNAi screen identifies an essential role for inositol pyrophosphates in Type-I interferon response. Pulloor NK, Nair S, McCaffrey K, Kostic AD, Bist P, Weaver JD, Riley AM, Tyagi R, Uchil PD, York JD, Snyder SH, García-Sastre A, Potter BV, Lin R, Shears SB, Xavier RJ, Krishnan MN. PLoS Pathog 10 e1003981 (2014)
  4. Synthesis of unsymmetric diphospho-inositol polyphosphates. Capolicchio S, Thakor DT, Linden A, Jessen HJ. Angew Chem Int Ed Engl 52 6912-6916 (2013)
  5. PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains. Gokhale NA, Zaremba A, Janoshazi AK, Weaver JD, Shears SB. Biochem J 453 413-426 (2013)
  6. Understanding inositol pyrophosphate metabolism and function: kinetic characterization of the DIPPs. Kilari RS, Weaver JD, Shears SB, Safrany ST. FEBS Lett 587 3464-3470 (2013)
  7. Synthesis of densely phosphorylated bis-1,5-diphospho-myo-inositol tetrakisphosphate and its enantiomer by bidirectional P-anhydride formation. Capolicchio S, Wang H, Thakor DT, Shears SB, Jessen HJ. Angew Chem Int Ed Engl 53 9508-9511 (2014)
  8. Synthetic inositol phosphate analogs reveal that PPIP5K2 has a surface-mounted substrate capture site that is a target for drug discovery. Wang H, Godage HY, Riley AM, Weaver JD, Shears SB, Potter BV. Chem Biol 21 689-699 (2014)
  9. The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. Gu C, Nguyen HN, Hofer A, Jessen HJ, Dai X, Wang H, Shears SB. J Biol Chem 292 4544-4555 (2017)
  10. IP6K structure and the molecular determinants of catalytic specificity in an inositol phosphate kinase family. Wang H, DeRose EF, London RE, Shears SB. Nat Commun 5 4178 (2014)
  11. Inositol Hexakisphosphate Kinase 3 Regulates Metabolism and Lifespan in Mice. Moritoh Y, Oka M, Yasuhara Y, Hozumi H, Iwachidow K, Fuse H, Tozawa R. Sci Rep 6 32072 (2016)
  12. TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway. Ghoshal S, Zhu Q, Asteian A, Lin H, Xu H, Ernst G, Barrow JC, Xu B, Cameron MD, Kamenecka TM, Chakraborty A. Mol Metab 5 903-917 (2016)
  13. Analysis of Dictyostelium discoideum inositol pyrophosphate metabolism by gel electrophoresis. Pisani F, Livermore T, Rose G, Chubb JR, Gaspari M, Saiardi A. PLoS One 9 e85533 (2014)
  14. Inositol pyrophosphate synthesis by inositol hexakisphosphate kinase 1 is required for homologous recombination repair. Jadav RS, Chanduri MV, Sengupta S, Bhandari R. J Biol Chem 288 3312-3321 (2013)
  15. The Vip1 inositol polyphosphate kinase family regulates polarized growth and modulates the microtubule cytoskeleton in fungi. Pöhlmann J, Risse C, Seidel C, Pohlmann T, Jakopec V, Walla E, Ramrath P, Takeshita N, Baumann S, Feldbrügge M, Fischer R, Fleig U. PLoS Genet 10 e1004586 (2014)
  16. Regulation of inositol metabolism is fine-tuned by inositol pyrophosphates in Saccharomyces cerevisiae. Ye C, Bandara WM, Greenberg ML. J Biol Chem 288 24898-24908 (2013)
  17. Asp1 Bifunctional Activity Modulates Spindle Function via Controlling Cellular Inositol Pyrophosphate Levels in Schizosaccharomyces pombe. Pascual-Ortiz M, Saiardi A, Walla E, Jakopec V, Künzel NA, Span I, Vangala A, Fleig U. Mol Cell Biol 38 e00047-18 (2018)
  18. Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling. Dollins DE, Bai W, Fridy PC, Otto JC, Neubauer JL, Gattis SG, Mehta KPM, York JD. Proc Natl Acad Sci U S A 117 9356-9364 (2020)
  19. Inositol pyrophosphates regulate RNA polymerase I-mediated rRNA transcription in Saccharomyces cerevisiae. Thota SG, Unnikannan CP, Thampatty SR, Manorama R, Bhandari R. Biochem J 466 105-114 (2015)
  20. The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment. Weaver JD, Wang H, Shears SB. Biosci Rep 33 e00022 (2013)
  21. Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse. Yousaf R, Gu C, Ahmed ZM, Khan SN, Friedman TB, Riazuddin S, Shears SB, Riazuddin S. PLoS Genet 14 e1007297 (2018)
  22. Inositol Polyphosphate Binding Specificity of the Jasmonate Receptor Complex. Laha D, Parvin N, Dynowski M, Johnen P, Mao H, Bitters ST, Zheng N, Schaaf G. Plant Physiol 171 2364-2370 (2016)
  23. First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP5 kinase. Riley AM, Wang H, Weaver JD, Shears SB, Potter BV. Chem Commun (Camb) 48 11292-11294 (2012)
  24. Use of Protein Kinase-Focused Compound Libraries for the Discovery of New Inositol Phosphate Kinase Inhibitors. Puhl-Rubio AC, Stashko MA, Wang H, Hardy PB, Tyagi V, Li B, Wang X, Kireev D, Jessen HJ, Frye SV, Shears SB, Pearce KH. SLAS Discov 23 982-988 (2018)
  25. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues. Hager A, Wu M, Wang H, Brown NW, Shears SB, Veiga N, Fiedler D. Chemistry 22 12406-12414 (2016)
  26. Synthetic tools for studying the chemical biology of InsP8. Riley AM, Wang H, Shears SB, L Potter BV. Chem Commun (Camb) 51 12605-12608 (2015)
  27. Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segregation Fidelity and Spindle Function in Schizosaccharomyces pombe. Topolski B, Jakopec V, Künzel NA, Fleig U. Mol Cell Biol 36 3128-3140 (2016)
  28. Activities and Structure-Function Analysis of Fission Yeast Inositol Pyrophosphate (IPP) Kinase-Pyrophosphatase Asp1 and Its Impact on Regulation of pho1 Gene Expression. Benjamin B, Garg A, Jork N, Jessen HJ, Schwer B, Shuman S. mBio 13 e0103422 (2022)
  29. Conformational changes in inositol 1,3,4,5,6-pentakisphosphate 2-kinase upon substrate binding: role of N-terminal lobe and enantiomeric substrate preference. Baños-Sanz JI, Sanz-Aparicio J, Whitfield H, Hamilton C, Brearley CA, González B. J Biol Chem 287 29237-29249 (2012)
  30. Development of Novel IP6K Inhibitors for the Treatment of Obesity and Obesity-Induced Metabolic Dysfunctions. Zhou Y, Mukherjee S, Huang D, Chakraborty M, Gu C, Zong G, Stashko MA, Pearce KH, Shears SB, Chakraborty A, Wang H, Wang X. J Med Chem 65 6869-6887 (2022)
  31. Identification of a functional nuclear translocation sequence in hPPIP5K2. Yong ST, Nguyen HN, Choi JH, Bortner CD, Williams J, Pulloor NK, Krishnan MN, Shears SB. BMC Cell Biol 16 17 (2015)
  32. New structural insights reveal an expanded reaction cycle for inositol pyrophosphate hydrolysis by human DIPP1. Zong G, Jork N, Hostachy S, Fiedler D, Jessen HJ, Shears SB, Wang H. FASEB J 35 e21275 (2021)
  33. The PPIP5K Family Member Asp1 Controls Inorganic Polyphosphate Metabolism in S. pombe. Pascual-Ortiz M, Walla E, Fleig U, Saiardi A. J Fungi (Basel) 7 626 (2021)
  34. Structural and catalytic analyses of the InsP6 kinase activities of higher plant ITPKs. Zong G, Shears SB, Wang H. FASEB J 36 e22380 (2022)
  35. The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function. Franco-Echevarría E, Sanz-Aparicio J, Brearley CA, González-Rubio JM, González B. J Biol Chem 292 10534-10548 (2017)
  36. PPIP5K1 Suppresses Etoposide-triggered Apoptosis. Machkalyan G, Hèbert TE, Miller GJ. J Mol Signal 11 4 (2016)
  37. Role of the inositol pyrophosphate multikinase Kcs1 in Cryptococcus inositol metabolism. Liao G, Wang Y, Liu TB, Kohli G, Qian W, Shor E, Subbian S, Xue C. Fungal Genet Biol 113 42-51 (2018)
  38. Synthesis of 2-diphospho-myo-inositol 1,3,4,5,6-pentakisphosphate and a photocaged analogue. Pavlovic I, Thakor DT, Jessen HJ. Org Biomol Chem 14 5559-5562 (2016)
  39. The Binding Mechanism Between Inositol Phosphate (InsP) and the Jasmonate Receptor Complex: A Computational Study. Cui M, Du J, Yao X. Front Plant Sci 9 963 (2018)
  40. Arabidopsis PFA-DSP-Type Phosphohydrolases Target Specific Inositol Pyrophosphate Messengers. Gaugler P, Schneider R, Liu G, Qiu D, Weber J, Schmid J, Jork N, Häner M, Ritter K, Fernández-Rebollo N, Giehl RFH, Trung MN, Yadav R, Fiedler D, Gaugler V, Jessen HJ, Schaaf G, Laha D. Biochemistry 61 1213-1227 (2022)
  41. Conformational stability of inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPK1) dictates its substrate selectivity. Gosein V, Miller GJ. J Biol Chem 288 36788-36795 (2013)
  42. Exploring the interaction mechanism between antagonist and the jasmonate receptor complex by molecular dynamics simulation. Cui M, Zhang K, Wu R, Du J. J Comput Aided Mol Des 36 141-155 (2022)
  43. The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis. Desfougères Y, Portela-Torres P, Qiu D, Livermore TM, Harmel RK, Borghi F, Jessen HJ, Fiedler D, Saiardi A. Adv Biol Regul 83 100835 (2022)
  44. A comparative metabolomics study on anadromous clupeid Tenualosa ilisha for better understanding the influence of habitat on nutritional composition. Ganguly S, Mitra T, Mahanty A, Mohanty S, Mohanty BP. Metabolomics 16 30 (2020)
  45. PPIP5K2 promotes colorectal carcinoma pathogenesis through facilitating DNA homologous recombination repair. Cao CH, Ling H, Han K, Lu XP, Cai MY, Cao JH, Zhou J, Xiang ZC, Chen JW, Li S, Lin JL, Duan JL, Luo J, Fang YJ, Pan ZZ, Liang L, Wang F, Xie D, Wang FW. Oncogene 40 6680-6691 (2021)
  46. Fluorination Influences the Bioisostery of Myo-Inositol Pyrophosphate Analogs. Hostachy S, Wang H, Zong G, Franke K, Riley AM, Schmieder P, Potter BVL, Shears SB, Fiedler D. Chemistry 29 e202302426 (2023)
  47. Inositol Pyrophosphate-Controlled Kinetochore Architecture and Mitotic Entry in S. pombe. Kuenzel NA, Alcázar-Román AR, Saiardi A, Bartsch SM, Daunaraviciute S, Fiedler D, Fleig U. J Fungi (Basel) 8 933 (2022)
  48. Inositol polyphosphate multikinase modulates redox signaling through nuclear factor erythroid 2-related factor 2 and glutathione metabolism. Tyagi R, Chakraborty S, Tripathi SJ, Jung IR, Kim SF, Snyder SH, Paul BD. iScience 26 107199 (2023)
  49. Novel Substrates for Kinases Involved in the Biosynthesis of Inositol Pyrophosphates and Their Enhancement of ATPase Activity of a Kinase. Mohanrao R, Manorama R, Ganguli S, Madhusudhanan MC, Bhandari R, Sureshan KM. Molecules 26 3601 (2021)
  50. Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase. Sanchez AM, Schwer B, Jork N, Jessen HJ, Shuman S. mBio 14 e0205623 (2023)
  51. Assigning the Absolute Configuration of Inositol Poly- and Pyrophosphates by NMR Using a Single Chiral Solvating Agent. Ritter K, Jork N, Unmüßig AS, Köhn M, Jessen HJ. Biomolecules 13 1150 (2023)
  52. ITPK1 Regulates Jasmonate-Controlled Root Development in Arabidopsis thaliana. Pullagurla NJ, Shome S, Yadav R, Laha D. Biomolecules 13 1368 (2023)
  53. Inositol pyrophosphate dynamics reveals control of the yeast phosphate starvation program through 1,5-IP8 and the SPX domain of Pho81. Chabert V, Kim GD, Qiu D, Liu G, Michaillat Mayer L, Jamsheer K M, Jessen HJ, Mayer A. Elife 12 RP87956 (2023)
  54. Structures of Fission Yeast Inositol Pyrophosphate Kinase Asp1 in Ligand-Free, Substrate-Bound, and Product-Bound States. Benjamin B, Goldgur Y, Jork N, Jessen HJ, Schwer B, Shuman S. mBio 13 e0308722 (2022)


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