2oh0: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=2PY:(2S)-1-{[5-(1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}-3-[(7AS)-7AH-INDOL-3-YL]PROPAN-2-AMINE'>2PY</scene> | |LIGAND= <scene name='pdbligand=2PY:(2S)-1-{[5-(1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}-3-[(7AS)-7AH-INDOL-3-YL]PROPAN-2-AMINE'>2PY</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span> | ||
|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus]) | |GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2f7z|2F7Z]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oh0 OCA], [http://www.ebi.ac.uk/pdbsum/2oh0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oh0 RCSB]</span> | |||
}} | }} | ||
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[[Category: cAMP-dependent protein kinase]] | [[Category: cAMP-dependent protein kinase]] | ||
[[Category: Stoll, V S.]] | [[Category: Stoll, V S.]] | ||
[[Category: akt]] | [[Category: akt]] | ||
[[Category: protein kinase some]] | [[Category: protein kinase some]] | ||
''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 04:17:44 2008'' | ||
Revision as of 04:17, 31 March 2008
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| , resolution 2.20Å | |||||||
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| Ligands: | |||||||
| Gene: | PRKACA (Bos taurus) | ||||||
| Activity: | cAMP-dependent protein kinase, with EC number 2.7.11.11 | ||||||
| Related: | 2F7Z
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Protein Kinase A in complex with Pyridine-Pyrazolopyridine Based Inhibitors
OverviewOverview
Thr-211 is one of three different amino acid residues in the kinase domain of protein kinase B/Akt as compared to protein kinase A (PKA), a closely related analog in the same AGC family. In an attempt to improve the potency and selectivity of our indazole-pyridine series of Akt inhibitors over PKA, efforts have focused on the incorporation of a chemical functionality to interact with the hydroxy group of Thr-211. Several substituents including an oxygen anion, amino, and nitro groups have been introduced at the C-6 position of the indazole scaffold, leading to a significant drop in Akt potency. Incorporation of a nitrogen atom into the phenyl ring at the same position (i.e., 9f) maintained the Akt activity and, in some cases, improved the selectivity over PKA. The structure-activity relationships of the new pyridine-pyrazolopyridine series of Akt inhibitors and their structural features when bound to PKA are also discussed.
About this StructureAbout this Structure
2OH0 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
Design and synthesis of pyridine-pyrazolopyridine-based inhibitors of protein kinase B/Akt., Zhu GD, Gong J, Gandhi VB, Woods K, Luo Y, Liu X, Guan R, Klinghofer V, Johnson EF, Stoll VS, Mamo M, Li Q, Rosenberg SH, Giranda VL, Bioorg Med Chem. 2007 Mar 15;15(6):2441-52. Epub 2007 Jan 17. PMID:17258463
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