5dgh
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with AMP-PNP and 5-(PCP)-IP5== | |
| + | <StructureSection load='5dgh' size='340' side='right' caption='[[5dgh]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5dgh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DGH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DGH FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5A3:METHYLENEBISPHOSPHONATE+INOSITOL+PENTAKISPHOSPHATE'>5A3</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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">[[5dgi|5dgi]]</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=5dgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dgh OCA], [http://pdbe.org/5dgh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dgh RCSB], [http://www.ebi.ac.uk/pdbsum/5dgh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dgh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. | ||
| - | + | Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.,Hager A, Wu M, Wang H, Brown NW Jr, Shears SB, Veiga N, Fiedler D Chemistry. 2016 Jul 27. doi: 10.1002/chem.201601754. PMID:27460418<ref>PMID:27460418</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: Shears, S | + | <div class="pdbe-citations 5dgh" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Shears, S B]] | ||
[[Category: Wang, H]] | [[Category: Wang, H]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase inositol diphosphoinositol pentakisphosphate kinase analog methylenebisphosphonate ppip5k atp-grasp pyrophosphate diphosphate]] | ||
Revision as of 15:50, 10 August 2016
Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with AMP-PNP and 5-(PCP)-IP5
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