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1uu7

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1uu7, resolution 1.90Å ()
Ligands: , ,
Non-Standard Residues:
Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Related: 1h1w, 1oky, 1okz, 1uu3, 1uu8, 1uu9, 1uvr
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH BIM-2

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

1uu7 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Komander D, Kular GS, Schuttelkopf AW, Deak M, Prakash KR, Bain J, Elliott M, Garrido-Franco M, Kozikowski AP, Alessi DR, van Aalten DM. Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1. Structure. 2004 Feb;12(2):215-26. PMID:14962382 doi:10.1016/j.str.2004.01.005

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