2jdo
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 2jdo |SIZE=350|CAPTION= <scene name='initialview01'>2jdo</scene>, resolution 1.80Å | |PDB= 2jdo |SIZE=350|CAPTION= <scene name='initialview01'>2jdo</scene>, resolution 1.80Å | ||
|SITE= <scene name='pdbsite=AC1:Edo+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Edo+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=I5S:ISOQUINOLINE-5-SULFONIC+ACID+(2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE'>I5S</scene> | + | |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> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |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> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Diabetes mellitus, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164731 164731]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 38: | Line 38: | ||
[[Category: Woodhead, S J.]] | [[Category: Woodhead, S J.]] | ||
[[Category: Workman, P.]] | [[Category: Workman, P.]] | ||
| - | [[Category: EDO]] | ||
| - | [[Category: I5S]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
| Line 49: | Line 47: | ||
[[Category: wnt signaling pathway]] | [[Category: wnt signaling pathway]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:56:42 2008'' |
Revision as of 00:56, 31 March 2008
| |||||||
| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF PKB-BETA (AKT2) COMPLEXED WITH ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY) ETHYLAMINO)ETHYL) AMIDE
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
2JDO is a Protein complex structure of sequences from Homo sapiens. 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 Mar 31 03:56:42 2008
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. | Alternative splicing | Atp-binding | Kinase | Nucleotide-binding | Phosphorylation | Serine/threonine-protein kinase | Transferase | Wnt signaling pathway
