関連する実験動画
Updated: Jul 7, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
p300/CBPトランスクリプションコアクティベーターによるタンパク質アセチル化の構造的基礎
Xin Liu1, Ling Wang, Kehao Zhao
1Program in Gene Expression and Regulation, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Nature
|February 15, 2008
まとめ
p300/CBP (CREBBP) ヒストンアセチルトランスフェラーゼ (HAT) 構造は,ユニークな触媒機構を明らかにしています. この発見は,がんなどの病気を標的としたエピジェネティック療法に新たな道を開く.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- エピジェネティクス エピジェネティクス
背景:
- p300/CBP (CREBBP) は,重要な転写共同活性化剤であり,ヒストンアセチルトランスフェラーゼ (HAT) である.
- 調節不良のHAT活動は,がんを含む疾患に関与しています.
- p300/CBPのメカニズムと構造に関する以前の研究では,矛盾する結果が得られました.
研究 の 目的:
- p300 HATドメインの高解像度構造を解明する.
- p300/CBPの触媒機構と基板特異性を理解する.
- 病気に関連した変異の構造的基礎を提供し,治療戦略を導く.
主な方法:
- p300 HATドメイン複合体の高解像度のX線結晶学.
- バイオケミカルアッセイと阻害剤の研究.
- シーケンスアラインメントと比較構造分析.
主要な成果:
- 新しい異体 p300 HAT ドメイン構造は,Lys-CoA.複合体で決定されました.
- 構造は,p300/CBPが,他の既知のHATと構造的に異なることを明らかにします.
- 新しい特徴は,基質の広範囲の特異性と,基本的残留物の好みを説明する.
- 他のHATとは異なる,異常な"ヒット・アンド・ラン"触媒機構が提案されています.
- 病気に関連した変異は,決定された構造によって容易に説明されます.
結論:
- p300 HAT構造は,その機能とメカニズムについて前例のない洞察を提供します.
- この研究は,p300/CBPのユニークな触媒戦略と基板相互作用を明らかにしています.
- この発見は,p300/CBP関連疾患に対する標的化された表遺伝子療法の開発を容易にする.
関連する概念動画
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...