2jdr

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spinqualitylabelsall models PDB ID 2jdr Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.30Å
Sites:
Ligands:	,
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH THE INHIBITOR A-443654

Overview

Although the crystal structure of the anti-cancer target protein kinase B (PKBbeta/Akt-2) has been useful in guiding inhibitor design, the closely related kinase PKA has generally been used as a structural mimic due to its facile crystallization with a range of ligands. The use of PKB-inhibitor crystallography would bring important benefits, including a more rigorous understanding of factors dictating PKA/PKB selectivity, and the opportunity to validate the utility of PKA-based surrogates. We present a "back-soaking" method for obtaining PKBbeta-ligand crystal structures, and provide a structural comparison of inhibitor binding to PKB, PKA, and PKA-PKB chimera. One inhibitor presented here exhibits no PKB/PKA selectivity, and the compound adopts a similar binding mode in all three systems. By contrast, the PKB-selective inhibitor A-443654 adopts a conformation in PKB and PKA-PKB that differs from that with PKA. We provide a structural explanation for this difference, and highlight the ability of PKA-PKB to mimic the true PKB binding mode in this case.

About this Structure

2JDR is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A structural comparison of inhibitor binding to PKB, PKA and PKA-PKB chimera., Davies TG, Verdonk ML, Graham B, Saalau-Bethell S, Hamlett CC, McHardy T, Collins I, Garrett MD, Workman P, Woodhead SJ, Jhoti H, Barford D, J Mol Biol. 2007 Mar 30;367(3):882-94. Epub 2007 Jan 9. PMID:17275837

Page seeded by OCA on Mon Mar 31 03:56:42 2008