2chx
From Proteopedia
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| - | [[Image:2chx.gif|left|200px]]<br /> | + | [[Image:2chx.gif|left|200px]]<br /><applet load="2chx" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2chx" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="2chx, resolution 2.500Å" /> | caption="2chx, resolution 2.500Å" /> | ||
'''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 /> | '''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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==About this Structure== | ==About this Structure== | ||
| - | 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 090 as [http://en.wikipedia.org/wiki/ligand ligand]. | + | 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 090 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CHX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:23:26 2007'' |
Revision as of 17:13, 18 December 2007
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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
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 with 090 as ligand. Known structural/functional Site: . 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
Page seeded by OCA on Tue Dec 18 19:23:26 2007
Categories: Homo sapiens | Single protein | Balla, A. | Balla, T. | Feldman, M.E. | Goldenberg, D.D. | Gonzalez, B. | Knight, Z.A. | Loewith, R. | Shokat, K.M. | Stokoe, D. | Toth, B. | Weiss, W.A. | Williams, O. | Williams, R.L. | Zunder, E.R. | 090 | 3-kinase | Inhibitor | Kinase | Lipid | Phosphoinositide | Quinazolinone | Signaling | Transferase
