2vnw: Difference between revisions

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[[Image:2vnw.~~jpg~~|left|200px]]

[[Image:2vnw.png|left|200px]]

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~~'''~~STRUCTURE OF PKA-PKB CHIMERA COMPLEXED WITH (1-(9H-PURIN-6-YL)PIPERIDIN-4-YL)METHANAMINE~~'''~~

===STRUCTURE OF PKA-PKB CHIMERA COMPLEXED WITH (1-(9H-PURIN-6-YL)PIPERIDIN-4-YL)METHANAMINE===

~~==Overview==~~

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~~Fragment~~-~~based screening identified 7~~-~~azaindole as a protein kinase B inhibitor scaffold. Fragment elaboration using iterative crystallography of inhibitor-PKA-PKB chimera complexes efficiently guided improvements in~~ the ~~potency and selectivity of~~ the ~~compounds, resulting in the identification of nanomolar 6-~~(~~piperidin-1-yl)purine, 4-(piperidin-1-yl~~)~~-7-azaindole~~, ~~and 4-(piperidin-1-yl)pyrrolo[2,3- d]pyrimidine inhibitors of PKBbeta with antiproliferative activity and showing pathway inhibition in cells. A divergence in~~ the ~~binding mode was seen between 4-aminomethylpiperidine and 4-aminopiperidine containing molecules~~. ~~Selectivity for PKB vs PKA was observed with 4~~-~~aminopiperidine derivatives, and the most PKB~~-~~selective inhibitor (30-fold) showed significantly different bound conformations between PKA and PKA-PKB chimera.~~

The line below this paragraph, {{ABSTRACT_PUBMED_18345609}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 18345609 is the PubMed ID number.

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==About this Structure==

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[[Category: Serine/threonine-protein kinase]]

[[Category: Transferase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Apr 30 13~~:34:09 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:11:10 2008''

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-[[Image:2vnw.jpg|left|200px]]
+{{Seed}}
+[[Image:2vnw.png|left|200px]]
 <!--
@@ Line 9: / Line 10: @@
 {{STRUCTURE_2vnw|  PDB=2vnw  |  SCENE=  }}
-'''STRUCTURE OF PKA-PKB CHIMERA COMPLEXED WITH (1-(9H-PURIN-6-YL)PIPERIDIN-4-YL)METHANAMINE'''
+===STRUCTURE OF PKA-PKB CHIMERA COMPLEXED WITH (1-(9H-PURIN-6-YL)PIPERIDIN-4-YL)METHANAMINE===
-==Overview==
+<!--
-Fragment-based screening identified 7-azaindole as a protein kinase B inhibitor scaffold. Fragment elaboration using iterative crystallography of inhibitor-PKA-PKB chimera complexes efficiently guided improvements in the potency and selectivity of the compounds, resulting in the identification of nanomolar 6-(piperidin-1-yl)purine, 4-(piperidin-1-yl)-7-azaindole, and 4-(piperidin-1-yl)pyrrolo[2,3- d]pyrimidine inhibitors of PKBbeta with antiproliferative activity and showing pathway inhibition in cells. A divergence in the binding mode was seen between 4-aminomethylpiperidine and 4-aminopiperidine containing molecules. Selectivity for PKB vs PKA was observed with 4-aminopiperidine derivatives, and the most PKB-selective inhibitor (30-fold) showed significantly different bound conformations between PKA and PKA-PKB chimera.
+The line below this paragraph, {{ABSTRACT_PUBMED_18345609}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 18345609 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_18345609}}
 ==About this Structure==
@@ Line 49: / Line 53: @@
 [[Category: Serine/threonine-protein kinase]]
 [[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:34:09 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:11:10 2008''