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| | ==Crystal structure of the catalytic domain of human type II alpha Phosphatidylinositol 4-kinase (PI4KIIalpha) in complex with ADP== | | ==Crystal structure of the catalytic domain of human type II alpha Phosphatidylinositol 4-kinase (PI4KIIalpha) in complex with ADP== |
| - | <StructureSection load='4hne' size='340' side='right' caption='[[4hne]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='4hne' size='340' side='right'caption='[[4hne]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HNE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HNE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hnd|4hnd]]</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=4hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hne OCA], [https://pdbe.org/4hne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hne RCSB], [https://www.ebi.ac.uk/pdbsum/4hne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hne ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PI4K2A, PI4KIIA (AMINO ACIDS 78-453) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-phosphatidylinositol_4-kinase 1-phosphatidylinositol 4-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.67 2.7.1.67] </span></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=4hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hne OCA], [http://pdbe.org/4hne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hne RCSB], [http://www.ebi.ac.uk/pdbsum/4hne PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hne ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/P4K2A_HUMAN P4K2A_HUMAN]] Together with PI4K2B and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells (By similarity). This lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P) producer in the Golgi apparatus, it generates more than 50% of this molecule which is essential for the identity of the organelle, protein sorting and membrane trafficking. | + | [https://www.uniprot.org/uniprot/P4K2A_HUMAN P4K2A_HUMAN] Together with PI4K2B and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells (By similarity). This lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P) producer in the Golgi apparatus, it generates more than 50% of this molecule which is essential for the identity of the organelle, protein sorting and membrane trafficking. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4hne" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4hne" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphatidylinositol 4-kinase|Phosphatidylinositol 4-kinase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 1-phosphatidylinositol 4-kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, C]] | + | [[Category: Chen C]] |
| - | [[Category: Sun, F]] | + | [[Category: Sun F]] |
| - | [[Category: Zhai, Y]] | + | [[Category: Zhai Y]] |
| - | [[Category: Zhang, K]] | + | [[Category: Zhang K]] |
| - | [[Category: Zhou, Q]] | + | [[Category: Zhou Q]] |
| - | [[Category: Atp binding]]
| + | |
| - | [[Category: Lipid kinase]]
| + | |
| - | [[Category: Membrane anchoring]]
| + | |
| - | [[Category: Palmitoylation]]
| + | |
| - | [[Category: Pi3k/pi4k kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
P4K2A_HUMAN Together with PI4K2B and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells (By similarity). This lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P) producer in the Golgi apparatus, it generates more than 50% of this molecule which is essential for the identity of the organelle, protein sorting and membrane trafficking.
Publication Abstract from PubMed
Phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), a membrane-associated PI kinase, plays a central role in cell signalling and trafficking. Its kinase activity critically depends on palmitoylation of its cysteine-rich motif (-CCPCC-) and is modulated by the membrane environment. Lack of atomic structure impairs our understanding of the mechanism regulating kinase activity. Here we present the crystal structure of human PI4KIIalpha in ADP-bound form. The structure identifies the nucleotide-binding pocket that differs notably from that found in PI3Ks. Two structural insertions, a palmitoylation insertion and an RK-rich insertion, endow PI4KIIalpha with the 'integral' membrane-binding feature. Molecular dynamics simulations, biochemical and mutagenesis studies reveal that the palmitoylation insertion, containing an amphipathic helix, contributes to the PI-binding pocket and anchors PI4KIIalpha to the membrane, suggesting that fluctuation of the palmitoylation insertion affects PI4KIIalpha's activity. We conclude from our results that PI4KIIalpha's activity is regulated indirectly through changes in the membrane environment.
Molecular insights into the membrane-associated phosphatidylinositol 4-kinase IIalpha.,Zhou Q, Li J, Yu H, Zhai Y, Gao Z, Liu Y, Pang X, Zhang L, Schulten K, Sun F, Chen C Nat Commun. 2014 Mar 28;5:3552. doi: 10.1038/ncomms4552. PMID:24675427[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhou Q, Li J, Yu H, Zhai Y, Gao Z, Liu Y, Pang X, Zhang L, Schulten K, Sun F, Chen C. Molecular insights into the membrane-associated phosphatidylinositol 4-kinase IIalpha. Nat Commun. 2014 Mar 28;5:3552. doi: 10.1038/ncomms4552. PMID:24675427 doi:http://dx.doi.org/10.1038/ncomms4552
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