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2x38

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Revision as of 09:27, 3 October 2018

The crystal structure of the murine class IA PI 3-kinase p110delta in complex with IC87114.

Structural highlights

2x38 is a 1 chain structure with sequence from Lk3 transgenic mice. This structure supersedes the now removed PDB entry 2wxe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Phosphatidylinositol-4,5-bisphosphate 3-kinase, with EC number 2.7.1.153
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat Chem Biol. 2010 Feb;6(2):117-24. PMID:20081827 doi:10.1038/nchembio.293

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2x38"

@@ Line 1: / Line 1: @@
-==THE CRYSTAL STRUCTURE OF THE MURINE CLASS IA PI 3-KINASE P110DELTA IN COMPLEX WITH IC87114.==
+==The crystal structure of the murine class IA PI 3-kinase p110delta in complex with IC87114.==
 <StructureSection load='2x38' size='340' side='right' caption='[[2x38]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IC8:2-[(6-AMINO-9H-PURIN-9-YL)METHYL]-5-METHYL-3-(2-METHYLPHENYL)QUINAZOLIN-4(3H)-ONE'>IC8</scene></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=2x38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x38 OCA], [http://pdbe.org/2x38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x38 RCSB], [http://www.ebi.ac.uk/pdbsum/2x38 PDBsum]</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=2x38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x38 OCA], [http://pdbe.org/2x38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x38 RCSB], [http://www.ebi.ac.uk/pdbsum/2x38 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x38 ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 11: / Line 12: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x3/2x38_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x3/2x38_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2x38

From Proteopedia

Revision as of 09:27, 3 October 2018

The crystal structure of the murine class IA PI 3-kinase p110delta in complex with IC87114.

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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