View source for 2wxq


==THE CRYSTAL STRUCTURE OF THE MURINE CLASS IA PI 3-KINASE P110DELTA IN COMPLEX WITH AS15.==
<StructureSection load='2wxq' size='340' side='right' caption='[[2wxq]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wxq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WXQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZZQ:2-{[3-(2-METHOXYPHENYL)-4-OXO-3,4,5,6,7,8-HEXAHYDROQUINAZOLIN-2-YL]SULFANYL}-N-QUINOXALIN-6-YLACETAMIDE'>ZZQ</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wxm|2wxm]], [[2wxh|2wxh]], [[2wxk|2wxk]], [[2wxl|2wxl]], [[2wxg|2wxg]], [[2wxi|2wxi]], [[2wxp|2wxp]], [[2wxo|2wxo]], [[2wxf|2wxf]], [[2wxn|2wxn]], [[2wxe|2wxe]], [[2wxj|2wxj]], [[2wxr|2wxr]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </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=2wxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wxq OCA], [http://pdbe.org/2wxq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wxq RCSB], [http://www.ebi.ac.uk/pdbsum/2wxq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wxq ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wx/2wxq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wxq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies.

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.,Berndt A, Miller S, Williams O, Le DD, Houseman BT, Pacold JI, Gorrec F, Hon WC, Liu Y, Rommel C, Gaillard P, Ruckle T, Schwarz MK, Shokat KM, Shaw JP, Williams RL Nat Chem Biol. 2010 Feb;6(2):117-24. PMID:20081827<ref>PMID:20081827</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2wxq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
[[Category: Berndt, A]]
[[Category: Gaillard, P]]
[[Category: Gorrec, F]]
[[Category: Hon, W C]]
[[Category: Houseman, B T]]
[[Category: Lee, D D]]
[[Category: Liu, Y]]
[[Category: Miller, S]]
[[Category: Pacold, J I]]
[[Category: Rommel, C]]
[[Category: Ruckle, T]]
[[Category: Schwarz, M K]]
[[Category: Shaw, J P]]
[[Category: Shokat, K M]]
[[Category: Williams, O]]
[[Category: Williams, R L]]
[[Category: Cancer]]
[[Category: Isoform-specific inhibitor]]
[[Category: Phosphoprotein]]
[[Category: Transferase]]