This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2d82
From Proteopedia
(New page: 200px<br /> <applet load="2d82" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d82" /> '''Target Structure-Based Discovery of Small M...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2d82.gif|left|200px]]<br /> | + | [[Image:2d82.gif|left|200px]]<br /><applet load="2d82" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2d82" size=" | + | |
caption="2d82" /> | caption="2d82" /> | ||
'''Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association'''<br /> | '''Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Lysine acetylation of human tumor suppressor p53 in response to cellular | + | 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. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2D82 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with TTR as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2D82 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=TTR:'>TTR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D82 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Liu, W | + | [[Category: Liu, W J.]] |
| - | [[Category: Manfredi, J | + | [[Category: Manfredi, J J.]] |
[[Category: Mujtaba, S.]] | [[Category: Mujtaba, S.]] | ||
[[Category: Resnick-Silverman, L.]] | [[Category: Resnick-Silverman, L.]] | ||
| Line 25: | Line 24: | ||
[[Category: Yan, S.]] | [[Category: Yan, S.]] | ||
[[Category: Zeng, L.]] | [[Category: Zeng, L.]] | ||
| - | [[Category: Zhou, M | + | [[Category: Zhou, M M.]] |
[[Category: TTR]] | [[Category: TTR]] | ||
[[Category: 3]] | [[Category: 3]] | ||
| Line 38: | Line 37: | ||
[[Category: p53]] | [[Category: p53]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:56:04 2008'' |
Revision as of 14:56, 21 February 2008
|
Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association
Contents |
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.
Disease
Known diseases associated with this structure: Blue-cone monochromacy OMIM:[303900], Colorblindness, protan OMIM:[303900], Rubenstein-Taybi syndrome OMIM:[600140]
About this Structure
2D82 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Histone acetyltransferase, with EC number 2.3.1.48 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 Thu Feb 21 16:56:04 2008
Categories: Histone acetyltransferase | Homo sapiens | Single protein | Liu, W J. | Manfredi, J J. | Mujtaba, S. | Resnick-Silverman, L. | Sachchidanand | Yan, S. | Zeng, L. | Zhou, M M. | TTR | 3 | 4 | 9-acetyl-2 | 9-tetrahydro-carbazol-1-one | Bromodomain | Cbp | Chemical ligand | Creb | Nmr structure | P53
