Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups.
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 (IP 5) and inositol hexakisphosphate (IP 6) 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 IP 5 and IP 6. 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.
Draskovic
Petra
P
Department of Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
Saiardi
Adolfo
A
Bhandari
Rashna
R
Burton
Adam
A
Ilc
Gregor
G
Kovacevic
Miroslav
M
Snyder
Solomon H
SH
Podobnik
Marjetka
M
D002101:Cacodylic Acid / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D011756:Diphosphates / Q000032:analysis* / Q000737:chemistry*; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D013058:Mass Spectrometry; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010833:Phytic Acid / Q000737:chemistry / Q000378:metabolism; D011122:Polyphosphates / Q000032:analysis* / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013379:Substrate Specificity
D011756:Diphosphates; D007295:Inositol Phosphates; D007527:Isoenzymes; D011122:Polyphosphates; C402123:inositol heptakisphosphate; C079849:1-diphosphoinositol pentakisphosphate; D010833:Phytic Acid; D002101:Cacodylic Acid; D017856:Phosphotransferases (Phosphate Group Acceptor); C099438:inositol hexakisphosphate kinase; C005692:triphosphoric acid