1e8w: Difference between revisions
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==Overview== | ==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, . | 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== | ==About this Structure== | ||
1E8W is a | 1E8W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with QUE as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] Structure known Active Site: QUE. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1E8W OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: secondary messenger generation]] | [[Category: secondary messenger generation]] | ||
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