2d82
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=TTR:9-ACETYL-2,3,4,9-TETRAHYDRO-1H-CARBAZOL-1-ONE'>TTR</scene> | |LIGAND= <scene name='pdbligand=TTR:9-ACETYL-2,3,4,9-TETRAHYDRO-1H-CARBAZOL-1-ONE'>TTR</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1jsp|1jsp]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2d82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d82 OCA], [http://www.ebi.ac.uk/pdbsum/2d82 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2d82 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Blue-cone monochromacy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=303900 303900]], Colorblindness, protan OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=303900 303900]], Rubenstein-Taybi syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600140 600140]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Zeng, L.]] | [[Category: Zeng, L.]] | ||
[[Category: Zhou, M M.]] | [[Category: Zhou, M M.]] | ||
| - | + | [[Category: 9-acetyl-2,3,4,9-tetrahydro-carbazol-1-one]] | |
| - | + | ||
| - | + | ||
| - | [[Category: 9-acetyl-2 | + | |
| - | + | ||
[[Category: bromodomain]] | [[Category: bromodomain]] | ||
[[Category: cbp]] | [[Category: cbp]] | ||
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[[Category: p53]] | [[Category: p53]] | ||
| - | ''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 02:31:11 2008'' |
Revision as of 23:31, 30 March 2008
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| Ligands: | |||||||
| Activity: | Histone acetyltransferase, with EC number 2.3.1.48 | ||||||
| Related: | 1jsp
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association
Overview
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.
About this Structure
2D82 is a Single protein structure of sequence from Homo sapiens. Full crystallographic 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
Page seeded by OCA on Mon Mar 31 02:31:11 2008
