2d82: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
|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> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==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. | ||
==About this Structure== | ==About this Structure== | ||
| Line 34: | Line 34: | ||
[[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]] | ||
| Line 46: | Line 42: | ||
[[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'' | ||
