6q73: Difference between revisions
New page: '''Unreleased structure''' The entry 6q73 is ON HOLD until Paper Publication Authors: Convery, M.A., Rowland, P., Down, K., Barton, N. Description: PI3K delta in complex with N[2chloro... |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==PI3K delta in complex with N[2chloro5(3,6dihydro2Hpyran4yl)pyridin3yl]methanesulfonamide== | ||
<StructureSection load='6q73' size='340' side='right'caption='[[6q73]], [[Resolution|resolution]] 2.21Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6q73]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q73 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]] 2.21Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HKK:~{N}-[2-chloranyl-5-(3,6-dihydro-2~{H}-pyran-4-yl)pyridin-3-yl]methanesulfonamide'>HKK</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=6q73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q73 OCA], [https://pdbe.org/6q73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q73 RCSB], [https://www.ebi.ac.uk/pdbsum/6q73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q73 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PK3CD_MOUSE PK3CD_MOUSE] Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function.<ref>PMID:12130661</ref> <ref>PMID:12235209</ref> <ref>PMID:15496927</ref> <ref>PMID:16116162</ref> <ref>PMID:18259608</ref> <ref>PMID:18809712</ref> <ref>PMID:19297623</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A deconstruction of previously reported PI3Kdelta inhibitors and subsequent regrowth led to the identification of a privileged fragment for PI3Kdelta which was exploited to deliver a potent, efficient and selective lead series with a novel binding mode observed in the PI3Kdelta crystal structure. | |||
Discovery of Potent, Efficient and Selective Inhibitors of Phosphoinositide 3-Kinase delta Through a Deconstruction and Regrowth Approach.,Barton N, Convery MA, Cooper AWJ, Down KD, Hamblin N, Inglis G, Peace S, Rowedder JE, Rowland P, Taylor JA, Wellaway N J Med Chem. 2018 Dec 11. doi: 10.1021/acs.jmedchem.8b01556. PMID:30532965<ref>PMID:30532965</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6q73" style="background-color:#fffaf0;"></div> | ||
[[Category: Barton | |||
[[Category: Convery | ==See Also== | ||
[[Category: Down | *[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Barton N]] | |||
[[Category: Convery MA]] | |||
[[Category: Down K]] | |||
[[Category: Rowland P]] | |||