2JDR: Structure Of Pkb-Beta (Akt2) Complexed With The Inhibitor A- 443654

Citation:
Abstract
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.
PDB ID: 2JDRDownload
MMDB ID: 44589
PDB Deposition Date: 2007/1/12
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 2JDR: dimeric; determined by author and by software (PQS)
Molecular Components in 2JDR
Label Count Molecule
Proteins (2 molecules)
1
Rac-beta Serine/threonine-protein Kinase(Gene symbol: AKT2)
Molecule annotation
1
Glycogen Synthase Kinase-3 Beta(Gene symbol: GSK3B)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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