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

doi:10.1016/j.chembiol.2008.01.011

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

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 language	English (US)
Pages (from-to)	274-286
Number of pages	13
Journal	Chemistry and Biology
Volume	15
Issue number	3
DOIs	https://doi.org/10.1016/j.chembiol.2008.01.011
State	Published - Mar 21 2008

Keywords

CHEMBIO
SIGNALING

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2008.01.011

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title = "Inositol Hexakisphosphate Kinase Products Contain Diphosphate and Triphosphate Groups",

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.",

keywords = "CHEMBIO, SIGNALING",

author = "Petra Dra{\v s}kovi{\v c} and Adolfo Saiardi and Rashna Bhandari and Adam Burton and Gregor Ilc and Miroslav Kova{\v c}evi{\v c} and Snyder, {Solomon H.} and Marjetka Podobnik",

note = "Funding Information: We acknowledge expert assistance from Aleksandar Ga{\'c}e{\v s}a, Primo{\v z} {\v S}ket, Mirko Cevec, Maja Capuder, and Bo{\v s}tjan Japelj. This work was supported by grants from the Slovenian Research Agency J4-6463 (M.P.), P1-0034 (M.K.), and 3311-04-831035 (P.D.); by Marie Curie International Re-Integration Grants No. 014882 (M.P.) and 014827 (A.S.); and by Medical Research Council funding of the Cell Biology Unit (A.S.). ",

year = "2008",

month = mar,

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doi = "10.1016/j.chembiol.2008.01.011",

language = "English (US)",

volume = "15",

pages = "274--286",

journal = "Chemistry and Biology",

issn = "1074-5521",

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T1 - Inositol Hexakisphosphate Kinase Products Contain Diphosphate and Triphosphate Groups

AU - Draškovič, Petra

AU - Saiardi, Adolfo

AU - Bhandari, Rashna

AU - Burton, Adam

AU - Ilc, Gregor

AU - Kovačevič, Miroslav

AU - Snyder, Solomon H.

AU - Podobnik, Marjetka

N1 - Funding Information: We acknowledge expert assistance from Aleksandar Gaćeša, Primož Šket, Mirko Cevec, Maja Capuder, and Boštjan Japelj. This work was supported by grants from the Slovenian Research Agency J4-6463 (M.P.), P1-0034 (M.K.), and 3311-04-831035 (P.D.); by Marie Curie International Re-Integration Grants No. 014882 (M.P.) and 014827 (A.S.); and by Medical Research Council funding of the Cell Biology Unit (A.S.).

PY - 2008/3/21

Y1 - 2008/3/21

N2 - 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.

AB - 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.

KW - CHEMBIO

KW - SIGNALING

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JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 3

ER -

Inositol Hexakisphosphate Kinase Products Contain Diphosphate and Triphosphate Groups

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