2chw

From Proteopedia

(Difference between revisions)

Revision as of 08:11, 23 May 2018

A pharmacological map of the PI3-K family defines a role for p110 alpha in signaling: The structure of complex of phosphoinositide 3- kinase gamma with inhibitor PIK-39

Structural highlights

2chw is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1e8y, 1e8z, 1he8, 2a4z, 2a5u, 2chx, 2chz
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

Phosphoinositide 3-kinases (PI3-Ks) are an important emerging class of drug targets, but the unique roles of PI3-K isoforms remain poorly defined. We describe here an approach to pharmacologically interrogate the PI3-K family. A chemically diverse panel of PI3-K inhibitors was synthesized, and their target selectivity was biochemically enumerated, revealing cryptic homologies across targets and chemotypes. Crystal structures of three inhibitors bound to p110gamma identify a conformationally mobile region that is uniquely exploited by selective compounds. This chemical array was then used to define the PI3-K isoforms required for insulin signaling. We find that p110alpha is the primary insulin-responsive PI3-K in cultured cells, whereas p110beta is dispensable but sets a phenotypic threshold for p110alpha activity. Compounds targeting p110alpha block the acute effects of insulin treatment in vivo, whereas a p110beta inhibitor has no effect. These results illustrate systematic target validation using a matrix of inhibitors that span a protein family.

A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.,Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B, Balla T, Weiss WA, Williams RL, Shokat KM Cell. 2006 May 19;125(4):733-47. Epub 2006 Apr 27. PMID:16647110^[1]

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

References

↑ Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B, Balla T, Weiss WA, Williams RL, Shokat KM. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47. Epub 2006 Apr 27. PMID:16647110 doi:http://dx.doi.org/10.1016/j.cell.2006.03.035

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/2chw"

@@ Line 1: / Line 1: @@
-==A PHARMACOLOGICAL MAP OF THE PI3-K FAMILY DEFINES A ROLE FOR P110 ALPHA IN SIGNALING: THE STRUCTURE OF COMPLEX OF PHOSPHOINOSITIDE 3-KINASE GAMMA WITH INHIBITOR PIK-39==
+==A pharmacological map of the PI3-K family defines a role for p110 alpha in signaling: The structure of complex of phosphoinositide 3- kinase gamma with inhibitor PIK-39==
 <StructureSection load='2chw' size='340' side='right' caption='[[2chw]], [[Resolution|resolution]] 2.60&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=039:2-((9H-PURIN-6-YLTHIO)METHYL)-5-CHLORO-3-(2-METHOXYPHENYL)QUINAZOLIN-4(3H)-ONE'>039</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1e8y|1e8y]], [[1e8z|1e8z]], [[1he8|1he8]], [[2a4z|2a4z]], [[2a5u|2a5u]], [[2chx|2chx]], [[2chz|2chz]]</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=2chw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2chw OCA], [http://pdbe.org/2chw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2chw RCSB], [http://www.ebi.ac.uk/pdbsum/2chw 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=2chw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2chw OCA], [http://pdbe.org/2chw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2chw RCSB], [http://www.ebi.ac.uk/pdbsum/2chw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2chw 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/ch/2chw_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2chw_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2chw

From Proteopedia

Revision as of 08:11, 23 May 2018

A pharmacological map of the PI3-K family defines a role for p110 alpha in signaling: The structure of complex of phosphoinositide 3- kinase gamma with inhibitor PIK-39

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox