1e7v
From Proteopedia
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'''STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE''' | '''STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE''' | ||
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[[Category: Williams, R L.]] | [[Category: Williams, R L.]] | ||
[[Category: Wymann, M P.]] | [[Category: Wymann, M P.]] | ||
| - | [[Category: | + | [[Category: Ly294002]] |
| - | [[Category: | + | [[Category: Phosphoinositide 3-kinase gamma]] |
| - | [[Category: | + | [[Category: Pi 3k]] |
| - | [[Category: | + | [[Category: Pi3k]] |
| - | [[Category: | + | [[Category: Secondary messenger generation]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:46:24 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:46, 2 May 2008
STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE
Overview
The specific phosphoinositide 3-kinase (PI3K) inhibitors wortmannin and LY294002 have been invaluable tools for elucidating the roles of these enzymes in signal transduction pathways. The X-ray crystallographic structures of PI3Kgamma bound to these lipid kinase inhibitors and to the broad-spectrum protein kinase inhibitors quercetin, myricetin, and staurosporine reveal how these compounds fit into the ATP binding pocket. With a nanomolar IC50, wortmannin most closely fits and fills the active site and induces a conformational change in the catalytic domain. Surprisingly, LY294002 and the lead compound on which it was designed, quercetin, as well as the closely related flavonoid myricetin bind PI3K in remarkably different orientations that are related to each other by 180 degrees rotations. Staurosporine/PI3K interactions are reminiscent of low-affinity protein kinase/staurosporine complexes. These results provide a rich basis for development of isoform-specific PI3K inhibitors with therapeutic potential.
About this Structure
1E7V is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine., Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL, Mol Cell. 2000 Oct;6(4):909-19. PMID:11090628 Page seeded by OCA on Fri May 2 14:46:24 2008
