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| | ==Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with AMPPNP and a substrate analog 5PA-IP5== | | ==Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with AMPPNP and a substrate analog 5PA-IP5== |
| - | <StructureSection load='4hn2' size='340' side='right' caption='[[4hn2]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4hn2' size='340' side='right'caption='[[4hn2]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hn2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4gb4 4gb4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HN2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hn2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4gb4 4gb4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HN2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0EJ:(2-OXO-2-{[(1S,2R,3S,4S,5R,6S)-2,3,4,5,6-PENTAKIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}ETHYL)PHOSPHONIC+ACID'>0EJ</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EJ:(2-OXO-2-{[(1S,2R,3S,4S,5R,6S)-2,3,4,5,6-PENTAKIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}ETHYL)PHOSPHONIC+ACID'>0EJ</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t9d|3t9d]], [[3t9b|3t9b]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hn2 OCA], [https://pdbe.org/4hn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hn2 RCSB], [https://www.ebi.ac.uk/pdbsum/4hn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hn2 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HISPPD1, KIAA0433, PPIP5K2, VIP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hn2 OCA], [http://pdbe.org/4hn2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hn2 RCSB], [http://www.ebi.ac.uk/pdbsum/4hn2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hn2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VIP2_HUMAN 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.<ref>PMID:17690096</ref> <ref>PMID:17702752</ref> | + | [https://www.uniprot.org/uniprot/VIP2_HUMAN 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.<ref>PMID:17690096</ref> <ref>PMID:17702752</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Wang, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Atp-grasp fold]] | + | [[Category: Wang H]] |
| - | [[Category: Inositol pyrophosphate kinase]]
| + | |
| - | [[Category: Phosphoryl transferase]]
| + | |
| - | [[Category: Pyrophosphate analog]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| 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
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