2d82: Difference between revisions
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New page: left|200px<br /> <applet load="2d82" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d82" /> '''Target Structure-Based Discovery of Small M... |
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[[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=" | |||
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'''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== | ||
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==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== | ||
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[[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.]] | ||
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[[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]] | ||
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[[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'' | ||
