View source for 4xz4


==Structure of PI3K gamma in complex with an inhibitor==
<StructureSection load='4xz4' size='340' side='right'caption='[[4xz4]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xz4]] is a 1 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=4XZ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XZ4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=456:N-[5-(6-METHOXYPYRAZIN-2-YL)-4,5,6,7-TETRAHYDRO[1,3]THIAZOLO[5,4-C]PYRIDIN-2-YL]ACETAMIDE'>456</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xx5|4xx5]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIK3CG ([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=4xz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xz4 OCA], [http://pdbe.org/4xz4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xz4 RCSB], [http://www.ebi.ac.uk/pdbsum/4xz4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xz4 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>  

==See Also==
*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Aronov, A M]]
[[Category: Bandarage, U K]]
[[Category: Boucher, C]]
[[Category: Collier, P N]]
[[Category: Come, J]]
[[Category: Cottrell, K M]]
[[Category: Damagnez, V]]
[[Category: Doran, J D]]
[[Category: Griffith, J P]]
[[Category: Khare-Pandit, S]]
[[Category: Krueger, E B]]
[[Category: Ledeboer, M W]]
[[Category: Ledford, B]]
[[Category: Liao, Y]]
[[Category: Mahajan, S]]
[[Category: Messersmith, D]]
[[Category: Moody, C S]]
[[Category: Tiran, A Le]]
[[Category: Wang, T]]
[[Category: Xu, J]]
[[Category: Inhibitor]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]