Structural highlights
Function
[VIP2_HUMAN] Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at positions 1 or 3 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates at position 1 or 3 PP-InsP5, produced by IP6Ks from InsP6, to produce (PP)2-InsP4.[1] [2]
Publication Abstract from PubMed
We synthesised analogues of diphosphoinositol polyphosphates (PP-InsPs) in which the diphosphate is replaced by an alpha-phosphonoacetic acid (PA) ester. Structural analysis revealed that 5-PA-InsP(5) mimics 5-PP-InsP(5) binding to the kinase domain of PPIP5K2; both molecules were phosphorylated by the enzyme. PA-InsPs are promising candidates for further studies into the biology of PP-InsPs.
First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP(5) kinase.,Riley AM, Wang H, Weaver JD, Shears SB, Potter BV Chem Commun (Camb). 2012 Oct 3. PMID:23032903[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fridy PC, Otto JC, Dollins DE, York JD. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J Biol Chem. 2007 Oct 19;282(42):30754-62. Epub 2007 Aug 9. PMID:17690096 doi:http://dx.doi.org/M704656200
- ↑ Choi JH, Williams J, Cho J, Falck JR, Shears SB. Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress. J Biol Chem. 2007 Oct 19;282(42):30763-75. Epub 2007 Aug 16. PMID:17702752 doi:http://dx.doi.org/M704655200
- ↑ Riley AM, Wang H, Weaver JD, Shears SB, Potter BV. First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP(5) kinase. Chem Commun (Camb). 2012 Oct 3. PMID:23032903 doi:http://dx.doi.org/10.1039/c2cc36044f
