6n5c
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the catalytic domain of PPIP5K2 in complex with AMPPNP and 5-PCF2Am-InsP5== | |
| + | <StructureSection load='6n5c' size='340' side='right'caption='[[6n5c]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6n5c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N5C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N5C FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=KDJ:(1,1-difluoro-2-oxo-2-{[(1s,2R,3S,4s,5R,6S)-2,3,4,5,6-pentakis(phosphonooxy)cyclohexyl]amino}ethyl)phosphonic+acid'>KDJ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6n5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n5c OCA], [http://pdbe.org/6n5c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n5c RCSB], [http://www.ebi.ac.uk/pdbsum/6n5c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n5c 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 == | ||
| + | Diphosphoinositol phosphates (PP-InsPs) are an evolutionarily ancient group of signalling molecules that are essential to cellular and organismal homeostasis. As the detailed mechanisms of PP-InsP signalling begin to emerge, synthetic analogues of PP-InsPs containing stabilised mimics of the labile diphosphate group can provide valuable investigational tools. We synthesised 5-PCF2Am-InsP5 (1), a novel fluorinated phosphonate analogue of 5-PP-InsP5, and obtained an X-ray crystal structure of 1 in complex with diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2). 5-PCF2Am-InsP5 binds to the kinase domain of PPIP5K2 in a similar orientation to that of the natural substrate 5-PP-InsP5 and the PCF2Am structure can mimic many aspects of the diphosphate group in 5-PP-InsP5. We propose that 1, the structural and electronic properties of which are in some ways complementary to those of existing phosphonoacetate and methylenebisphosphonate analogues of 5-PP-InsP5, may be a useful addition to the expanding array of chemical tools for the investigation of signalling by PP-InsPs. The PCF2Am group may also deserve attention for wider application as a diphosphate mimic. | ||
| - | + | Synthesis of an alpha-phosphono-alpha,alpha-difluoroacetamide analogue of the diphosphoinositol pentakisphosphate 5-InsP7.,Riley AM, Wang H, Shears SB, Potter BVL Medchemcomm. 2019 Jun 7;10(7):1165-1172. doi: 10.1039/c9md00163h. eCollection, 2019 Jul 1. PMID:31391889<ref>PMID:31391889</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 6n5c" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Potter, B]] | [[Category: Potter, B]] | ||
| + | [[Category: Riley, A]] | ||
| + | [[Category: Shears, S B]] | ||
| + | [[Category: Wang, H]] | ||
| + | [[Category: Analog]] | ||
| + | [[Category: Diphosphoinositol pentakisphosphate]] | ||
| + | [[Category: Inositol]] | ||
| + | [[Category: Inositol polyphosphate]] | ||
| + | [[Category: Inositol pyrophosphate]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Phosphonodifluoroacetamide]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 05:54, 21 August 2019
Crystal structure of the catalytic domain of PPIP5K2 in complex with AMPPNP and 5-PCF2Am-InsP5
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