Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition

Beatriz Gonzalez, Jose Ignacio Banos-Sanz, Maider Villate, Charles Alistair Brearley, Julia Sanz-Aparicio

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular Graphic (InsP6) is involved in mRNA export and editing or chromatin remodeling among other events. InsP6 accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP6 that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P5 2-kinase (InsP5 2-kinase or Ipk1) catalyses the synthesis of InsP6 from InsP5 and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP5 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates.
Original languageEnglish
Pages (from-to)9608-9613
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume107
Issue number21
Early online date7 May 2010
DOIs
Publication statusPublished - 25 May 2010

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