2chx

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[[Image:2chx.gif|left|200px]]<br /><applet load="2chx" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2chx.gif|left|200px]]
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caption="2chx, resolution 2.500&Aring;" />
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'''A PHARMACOLOGICAL MAP OF THE PI3-K FAMILY DEFINES A ROLE FOR P110ALPHA IN SIGNALING: THE STRUCTURE OF COMPLEX OF PHOSPHOINOSITIDE 3-KINASE GAMMA WITH INHIBITOR PIK-90'''<br />
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{{Structure
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|PDB= 2chx |SIZE=350|CAPTION= <scene name='initialview01'>2chx</scene>, resolution 2.500&Aring;
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|SITE= <scene name='pdbsite=AC1:090+Binding+Site+For+Chain+A'>AC1</scene>
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|LIGAND= <scene name='pdbligand=090:N-(2,3-DIHYDRO-7,8-DIMETHOXYIMIDAZO[1,2-C] QUINAZOLIN-5-YL)NICOTINAMIDE'>090</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''A PHARMACOLOGICAL MAP OF THE PI3-K FAMILY DEFINES A ROLE FOR P110ALPHA IN SIGNALING: THE STRUCTURE OF COMPLEX OF PHOSPHOINOSITIDE 3-KINASE GAMMA WITH INHIBITOR PIK-90'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2CHX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=090:'>090</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:090+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CHX OCA].
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2CHX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CHX OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16647110 16647110]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/16647110 16647110]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:48:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:15:39 2008''

Revision as of 14:15, 20 March 2008

Image:2chx.gif


PDB ID 2chx

Drag the structure with the mouse to rotate
, resolution 2.500Å
Sites:
Ligands:
Coordinates: save as pdb, mmCIF, xml



A PHARMACOLOGICAL MAP OF THE PI3-K FAMILY DEFINES A ROLE FOR P110ALPHA IN SIGNALING: THE STRUCTURE OF COMPLEX OF PHOSPHOINOSITIDE 3-KINASE GAMMA WITH INHIBITOR PIK-90


Overview

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.

About this Structure

2CHX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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