2jdo: Difference between revisions

Revision as of 08:44, 4 May 2008

STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY) ETHYLAMINO)ETHYL) AMIDE

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

2JDO is a Protein complex structure of sequences from Homo sapiens. 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 Sun May 4 08:44:41 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2jdo.gif|left|200px]]
- {{Structure
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+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=I5S:ISOQUINOLINE-5-SULFONIC+ACID+(2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE'>I5S</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jdo OCA], [http://www.ebi.ac.uk/pdbsum/2jdo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2jdo RCSB]</span>
-}}
 '''STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY) ETHYLAMINO)ETHYL) AMIDE'''
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 [[Category: Woodhead, S J.]]
 [[Category: Workman, P.]]
-[[Category: alternative splicing]]
+[[Category: Alternative splicing]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: kinase]]
+[[Category: Kinase]]
-[[Category: nucleotide-binding]]
+[[Category: Nucleotide-binding]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: serine/threonine-protein kinase]]
+[[Category: Serine/threonine-protein kinase]]
-[[Category: transferase]]
+[[Category: Transferase]]
-[[Category: wnt signaling pathway]]
+[[Category: Wnt signaling pathway]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:44:41 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:56:42 2008''