2d82

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spinqualitylabelsall models PDB ID 2d82 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
Ligands:
Activity:	Histone acetyltransferase, with EC number 2.3.1.48
Coordinates:	save as pdb, mmCIF, xml

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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. 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

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