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2jdr
From Proteopedia
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| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 18:32:08 2007'' |
Revision as of 16:26, 5 November 2007
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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 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.
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 Nov 5 18:32:08 2007
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Protein complex | Barford, D. | Collins, I. | Davies, T.G. | Garrett, M.D. | Graham, B. | Hamlett, C.C.F. | Jhoti, H. | Mchardy, T. | Saalau-Bethell, S. | Verdonk, M.L. | Woodhead, S.J. | Workman, P. | L20 | Alternative splicing | Atp-binding | Kinase | Nucleotide-binding | Phosphorylation | Serine/threonine-protein kinase | Transferase | Wnt signaling pathway
