3BIY

Crystal structure of p300 histone acetyltransferase domain in complex with a bisubstrate inhibitor, Lys-CoA

3BIY の概要

• エントリーDOI: 10.2210/pdb3biy/pdb
• 分子名称: Histone acetyltransferase p300, BROMIDE ION, [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]methyl (3R,20R)-20-carbamoyl-3-hydroxy-2,2-dimethyl-4,8,14,22-tetraoxo-12-thia-5,9,15,21-tetraazatricos-1-yl dihydrogen diphosphate, ... (4 entities in total)
• 機能のキーワード: p300 hat, bisubstrate inhibitor, protein-inhibitor complex, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q09472
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45370.24

構造登録者

Liu, X.,Wang, L.,Zhao, K.,Thompson, P.R.,Hwang, Y.,Marmorstein, R.,Cole, P.A. (登録日: 2007-12-02, 公開日: 2008-02-12, 最終更新日: 2024-02-21)

主引用文献

Liu, X.,Wang, L.,Zhao, K.,Thompson, P.R.,Hwang, Y.,Marmorstein, R.,Cole, P.A.
The structural basis of protein acetylation by the p300/CBP transcriptional coactivator
Nature, 451:846-850, 2008

PubMed Abstract: The transcriptional coactivator p300/CBP (CREBBP) is a histone acetyltransferase (HAT) that regulates gene expression by acetylating histones and other transcription factors. Dysregulation of p300/CBP HAT activity contributes to various diseases including cancer. Sequence alignments, enzymology experiments and inhibitor studies on p300/CBP have led to contradictory results about its catalytic mechanism and its structural relation to the Gcn5/PCAF and MYST HATs. Here we describe a high-resolution X-ray crystal structure of a semi-synthetic heterodimeric p300 HAT domain in complex with a bi-substrate inhibitor, Lys-CoA. This structure shows that p300/CBP is a distant cousin of other structurally characterized HATs, but reveals several novel features that explain the broad substrate specificity and preference for nearby basic residues. Based on this structure and accompanying biochemical data, we propose that p300/CBP uses an unusual 'hit-and-run' (Theorell-Chance) catalytic mechanism that is distinct from other characterized HATs. Several disease-associated mutations can also be readily accounted for by the p300 HAT structure. These studies pave the way for new epigenetic therapies involving modulation of p300/CBP HAT activity.

PubMed: 18273021
DOI: 10.1038/nature06546

実験手法

X-RAY DIFFRACTION (1.7 Å)