Journal
CHEMISTRY & BIOLOGY
Volume 15, Issue 3, Pages 274-286Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2008.01.011
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Funding
- MRC [MC_U122680443] Funding Source: UKRI
- Medical Research Council [MC_U122680443] Funding Source: Medline
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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.
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