1uu9: Difference between revisions
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==Overview== | ==Overview== | ||
LY333531, BIM-1, BIM-2, BIM-3, and BIM-8 are bisindolyl maleimide-based, nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific, inhibitor, is in clinical trials against diabetes and cardiac ventricular, hypertrophy complications. Specificity analysis with a panel of 29 protein, kinases reveals that these bisindolyl maleimide inhibitors also inhibit, PDK1, a key kinase from the insulin signaling pathway, albeit in the lower, microM range. To understand the molecular basis of inhibition, the PDK1, kinase domain was cocrystallized with these bisindolyl maleimide, inhibitors. The inhibitor complexes represent the first structural, description of this class of compounds, revealing their unusual nonplanar, conformation within the ATP binding site and also explaining the higher, .. | LY333531, BIM-1, BIM-2, BIM-3, and BIM-8 are bisindolyl maleimide-based, nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific, inhibitor, is in clinical trials against diabetes and cardiac ventricular, hypertrophy complications. Specificity analysis with a panel of 29 protein, kinases reveals that these bisindolyl maleimide inhibitors also inhibit, PDK1, a key kinase from the insulin signaling pathway, albeit in the lower, microM range. To understand the molecular basis of inhibition, the PDK1, kinase domain was cocrystallized with these bisindolyl maleimide, inhibitors. The inhibitor complexes represent the first structural, description of this class of compounds, revealing their unusual nonplanar, conformation within the ATP binding site and also explaining the higher, inhibitory potential of LY33331 compared to the BIM compounds toward PDK1., A combination of site-directed mutagenesis and essential dynamics analysis, gives further insight into PDK1 and also PKC inhibition by these, compounds, and may aid inhibitor design. | ||
==About this Structure== | ==About this Structure== | ||
1UU9 is a | 1UU9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda] with SO4, BI3 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Structure known Active Site: BC6. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UU9 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
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