View source for 4hnd


==Crystal structure of the catalytic domain of Selenomethionine substituted human PI4KIIalpha in complex with ADP==
<StructureSection load='4hnd' size='340' side='right'caption='[[4hnd]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hnd]] 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=4HND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HND FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</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>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=4hnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hnd OCA], [https://pdbe.org/4hnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hnd RCSB], [https://www.ebi.ac.uk/pdbsum/4hnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hnd ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== 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<ref>PMID:24675427</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4hnd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphatidylinositol 4-kinase|Phosphatidylinositol 4-kinase]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen C]]
[[Category: Sun F]]
[[Category: Zhai Y]]
[[Category: Zhang K]]
[[Category: Zhou Q]]