1uu9: Difference between revisions

Revision as of 19:02, 18 December 2007

STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH BIM-3

OverviewOverview

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 StructureAbout this Structure

1UU9 is a Single protein structure of sequence from Spodoptera frugiperda with SO4, BI3 and GOL as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1., Komander D, Kular GS, Schuttelkopf AW, Deak M, Prakash KR, Bain J, Elliott M, Garrido-Franco M, Kozikowski AP, Alessi DR, van Aalten DM, Structure. 2004 Feb;12(2):215-26. PMID:14962382

Page seeded by OCA on Tue Dec 18 18:12:24 2007

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OCA

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 ==About this Structure==
-UU9 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].
+UU9 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] Known structural/functional Site: <scene name='pdbsite=BC6:Bi3 Binding Site For Chain A'>BC6</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UU9 OCA].
 ==Reference==
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 [[Category: transferase]]
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