1e7u: Difference between revisions
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[[Image:1e7u.gif|left|200px]] | [[Image:1e7u.gif|left|200px]] | ||
'''STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE''' | {{Structure | ||
|PDB= 1e7u |SIZE=350|CAPTION= <scene name='initialview01'>1e7u</scene>, resolution 2.0Å | |||
|SITE= <scene name='pdbsite=KWT:Site+Of+Covalent+Attachment+Of+Wortmannin+To+Protein'>KWT</scene> | |||
|LIGAND= <scene name='pdbligand=KWT:(1S,6BR,9AS,11R,11BR)-9A,11B-DIMETHYL-1-[(METHYLOXY)METHYL]-3,6,9-TRIOXO-1,6,6B,7,8,9,9A,10,11,11B-DECAHYDRO-3H-FURO[4,3,2-DE]INDENO[4,5-H][2]BENZOPYRAN-11-YL ACETATE'>KWT</scene> | |||
|ACTIVITY= [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] | |||
|GENE= P120S144C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 Sus scrofa]) | |||
}} | |||
'''STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1E7U is a [ | 1E7U is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E7U OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11090628 11090628] | ||
[[Category: Phosphatidylinositol 3-kinase]] | [[Category: Phosphatidylinositol 3-kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: wortmannin]] | [[Category: wortmannin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:51:14 2008'' | ||
Revision as of 11:51, 20 March 2008
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| , resolution 2.0Å | |||||||
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| Sites: | |||||||
| Ligands: | |||||||
| Gene: | P120S144C (Sus scrofa) | ||||||
| Activity: | Phosphatidylinositol 3-kinase, with EC number 2.7.1.137 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE DETERMINANTS OF PHOSPHOINOSITIDE 3-KINASE INHIBITION BY WORTMANNIN, LY294002, QUERCETIN, MYRICETIN AND STAUROSPORINE
OverviewOverview
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 StructureAbout this Structure
1E7U is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
ReferenceReference
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
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