2ojf: Difference between revisions

Revision as of 11:02, 4 May 2008

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

2OJF 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 Page seeded by OCA on Sun May 4 11:02:18 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2ojf.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2ojf", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=4PY:(2S)-1-(6H-INDOL-3-YL)-3-{[5-(7H-PYRAZOLO[3,4-C]PYRIDIN-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE'>4PY</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/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>
+or leave the SCENE parameter empty for the default display.
-|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
+-->
-|DOMAIN=
+{{STRUCTURE_2ojf|  PDB=2ojf  |  SCENE=  }}
-|RELATEDENTRY=[[1oh0|1OH0]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ojf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ojf OCA], [http://www.ebi.ac.uk/pdbsum/2ojf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ojf RCSB]</span>
-}}
 '''Crystal structure of Protein Kinase A in complex with Pyridine-Pyrazolopyridine based inhibitors'''
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 [[Category: Bos taurus]]
 [[Category: Single protein]]
-[[Category: cAMP-dependent protein kinase]]
+[[Category: CAMP-dependent protein kinase]]
 [[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 Sun May  4 11:02:18 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:18:39 2008''