2jdr: Difference between revisions
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|PDB= 2jdr |SIZE=350|CAPTION= <scene name='initialview01'>2jdr</scene>, resolution 2.30Å | |PDB= 2jdr |SIZE=350|CAPTION= <scene name='initialview01'>2jdr</scene>, resolution 2.30Å | ||
|SITE= <scene name='pdbsite=AC1:L20+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:L20+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=L20:(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE'>L20</scene> | |LIGAND= <scene name='pdbligand=L20:(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE'>L20</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=2jdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jdr OCA], [http://www.ebi.ac.uk/pdbsum/2jdr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2jdr RCSB]</span> | |||
}} | }} | ||
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==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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Woodhead, S J.]] | [[Category: Woodhead, S J.]] | ||
[[Category: Workman, P.]] | [[Category: Workman, P.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
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[[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'' | ||
