Inositol Hexakisphosphate Kinase Products Contain Diphosphate and Triphosphate Groups

Petra Draškovič, Adolfo Saiardi, Rashna Bhandari, Adam Burton, Gregor Ilc, Miroslav Kovačevič, Solomon H. Snyder, Marjetka Podobnik

Research output: Contribution to journalArticlepeer-review

Abstract

Eukaryotic cells produce a family of diverse inositol polyphosphates (IPs) containing pyrophosphate bonds. Inositol pyrophosphates have been linked to a wide range of cellular functions, and there is growing evidence that they act as second messengers. Inositol hexakisphosphate kinase (IP6K) is able to convert the natural substrates inositol pentakisphosphate (IP5) and inositol hexakisphosphate (IP6) to several products with an increasing number of phospho-anhydride bonds. In this study, we structurally analyzed IPs synthesized by three mammalian isoforms of IP6K from IP5 and IP6. The NMR and mass analyses showed a number of products with diverse, yet specific, stereochemistry, defined by the architecture of IP6K's active site. We now report that IP6K synthesizes both pyrophosphate (diphospho) as well as triphospho groups on the inositol ring. All three IP6K isoforms share the same activities both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)274-286
Number of pages13
JournalChemistry and Biology
Volume15
Issue number3
DOIs
StatePublished - Mar 21 2008

Keywords

  • CHEMBIO
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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