2d82: Difference between revisions

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[[Image:2d82.gif|left|200px]]
{{Seed}}
[[Image:2d82.png|left|200px]]


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{{STRUCTURE_2d82|  PDB=2d82  |  SCENE=  }}  
{{STRUCTURE_2d82|  PDB=2d82  |  SCENE=  }}  


'''Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association'''
===Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association===




==Overview==
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Lysine acetylation of human tumor suppressor p53 in response to cellular stress signals is required for its function as a transcription factor that regulates cell cycle arrest, senescence, or apoptosis. Here, we report small molecules that block lysine 382-acetylated p53 association with the bromodomain of the coactivator CBP, an interaction essential for p53-induced transcription of the cell cycle inhibitor p21 in response to DNA damage. These chemicals were discovered in target structure-guided nuclear magnetic resonance spectroscopy screening of a focused chemical library constructed based on the structural knowledge of CBP bromodomain/p53-AcK382 binding. Structural characterization shows that these chemicals inhibit CBP/p53 association by binding to the acetyl-lysine binding site of the bromodomain. Cell-based functional assays demonstrate that the lead chemicals can modulate p53 stability and function in response to DNA damage.
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{{ABSTRACT_PUBMED_16426974}}


==About this Structure==
==About this Structure==
2D82 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D82 OCA].  
2D82 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D82 OCA].  


==Reference==
==Reference==
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[[Category: Nmr structure]]
[[Category: Nmr structure]]
[[Category: P53]]
[[Category: P53]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 23:50:39 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:10:52 2008''

Revision as of 11:10, 29 July 2008

File:2d82.png

Template:STRUCTURE 2d82

Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association

Template:ABSTRACT PUBMED 16426974

About this Structure

2D82 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Target structure-based discovery of small molecules that block human p53 and CREB binding protein association., Sachchidanand, Resnick-Silverman L, Yan S, Mutjaba S, Liu WJ, Zeng L, Manfredi JJ, Zhou MM, Chem Biol. 2006 Jan;13(1):81-90. PMID:16426974

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