2JDV

Structure of PKA-PKB chimera complexed with A-443654

Summary for 2JDV

• Entry DOI: 10.2210/pdb2jdv/pdb
• Related: 1CMK 1KMU 1KMW 1Q24 1Q61 1Q62 1Q8T 1Q8U 1Q8W 1SMH 1STC 1SVE 1SVG 1SVH 1SZM 1VEB 1XH4 1XH5 1XH6 1XH7 1XH8 1XH9 1XHA 1YDR 1YDS 1YDT 2C1A 2C1B 2F7E 2GFC 2GNF 2GNG 2GNH 2GNI 2GNJ 2GNL 2JDO 2JDR 2JDS 2JDT
• Descriptor: CAMP-DEPENDENT PROTEIN KINASE, CAMP-DEPENDENT PROTEIN KINASE INHIBITOR ALPHA, (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE, ... (4 entities in total)
• Functional Keywords: camp, kinase, myristate, transferase, lipoprotein, serine/threonine-protein kinase, nucleotide-binding, protein kinase inhibitor, atp-binding, nuclear protein, phosphorylation
• Biological source: BOS TAURUS (BOVINE); More
• Cellular location: Cytoplasm: P00517
• Total number of polymer chains: 2
• Total formula weight: 43454.50

Authors

Davies, T.G.,Verdonk, M.L.,Graham, B.,Saalau-Bethell, S.,Hamlett, C.C.F.,Mchardy, T.,Collins, I.,Garrett, M.D.,Workman, P.,Woodhead, S.J.,Jhoti, H.,Barford, D. (deposition date: 2007-01-12, release date: 2007-02-13, Last modification date: 2024-11-20)

Primary citation

Davies, T.G.,Verdonk, M.L.,Graham, B.,Saalau-Bethell, S.,Hamlett, C.C.F.,Mchardy, T.,Collins, I.,Garrett, M.D.,Workman, P.,Woodhead, S.J.,Jhoti, H.,Barford, D.
A Structural Comparison of Inhibitor Binding to Pkb, Pka and Pka-Pkb Chimera
J.Mol.Biol., 367:882-, 2007

PubMed 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.

PubMed: 17275837
DOI: 10.1016/J.JMB.2007.01.004

Experimental method

X-RAY DIFFRACTION (2.08 Å)