2jdr

File:2jdr.gif

spinqualitylabelsall models 2jdr, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

OverviewOverview

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 StructureAbout this Structure

2JDR is a Protein complex structure of sequences from Homo sapiens with L20 as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

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 Nov 5 14:11:07 2007