2f7x: Difference between revisions

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Revision as of 17:49, 20 March 2008

File:2f7x.gif

, resolution 1.90Å

Ligands:

Gene:

PRKACA (Bos taurus)

Activity:

Non-specific serine/threonine protein kinase, with EC number 2.7.11.1

Coordinates:

save as pdb, mmCIF, xml

Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine

OverviewOverview

A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.

About this StructureAbout this Structure

2F7X is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

ReferenceReference

Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation., Li Q, Li T, Zhu GD, Gong J, Claibone A, Dalton C, Luo Y, Johnson EF, Shi Y, Liu X, Klinghofer V, Bauch JL, Marsh KC, Bouska JJ, Arries S, De Jong R, Oltersdorf T, Stoll VS, Jakob CG, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1679-85. Epub 2006 Jan 5. PMID:16403626

Page seeded by OCA on Thu Mar 20 16:49:10 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2f7x.gif|left|200px]]<br /><applet load="2f7x" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2f7x.gif|left|200px]]
-caption="2f7x, resolution 1.90&Aring;" />
-'''Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine'''<br />
+ {{Structure
+|PDB= 2f7x |SIZE=350|CAPTION= <scene name='initialview01'>2f7x</scene>, resolution 1.90&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=4EA:(1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINE'>4EA</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]
+|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
+}}
+'''Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-F7X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=4EA:'>4EA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F7X OCA].
+F7X is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F7X OCA].
 ==Reference==
-Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation., Li Q, Li T, Zhu GD, Gong J, Claibone A, Dalton C, Luo Y, Johnson EF, Shi Y, Liu X, Klinghofer V, Bauch JL, Marsh KC, Bouska JJ, Arries S, De Jong R, Oltersdorf T, Stoll VS, Jakob CG, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1679-85. Epub 2006 Jan 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16403626 16403626]
+Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation., Li Q, Li T, Zhu GD, Gong J, Claibone A, Dalton C, Luo Y, Johnson EF, Shi Y, Liu X, Klinghofer V, Bauch JL, Marsh KC, Bouska JJ, Arries S, De Jong R, Oltersdorf T, Stoll VS, Jakob CG, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1679-85. Epub 2006 Jan 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16403626 16403626]
 [[Category: Bos taurus]]
 [[Category: Non-specific serine/threonine protein kinase]]
@@ Line 36: / Line 45: @@
 [[Category: Zhu, G D.]]
 [[Category: 4EA]]
-[[Category: akt inhibitors]]
+[[Category: akt inhibitor]]
-[[Category: protein kinase a]]
+[[Category: protein kinase some]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:18:35 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:49:10 2008''