相关实验视频
Updated: Jul 7, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
通过p300/CBP转录协活性器进行蛋白质乙化的结构基础
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
概括
在p300/CBP (CREBBP) 基因乙转移酶 (HAT) 结构中,发现了一个独特的催化机制. 这一发现为针对癌症等疾病的表观遗传疗法提供了新的途径.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- p300/CBP (CREBBP) 是一个关键的转录协激活剂和氨酸转移酶 (HAT).
- 失调的HAT活性与包括癌症在内的疾病有关.
- 之前对p300/CBP机制和结构的研究产生了相互矛盾的结果.
研究的目的:
- 为了阐明p300 HAT域的高分辨率结构.
- 了解p300/CBP的催化机制和基质特异性.
- 为疾病相关突变提供结构基础,并指导治疗策略.
主要方法:
- 一个p300 HAT域综合体的高分辨率X射线晶体学.
- 生物化学测定和抑制剂研究.
- 序列对齐和比较结构分析.
主要成果:
- 一个新的异构 p300 HAT 域结构与Lys-CoA.复合确定.
- 结构显示p300/CBP与其他已知的HAT结构不同.
- 新的特征解释了广泛的基质特异性和对基本残留物的偏好.
- 提出了一种不寻常的"撞逃"催化机制,与其他HAT不同.
- 与疾病相关的突变很容易通过确定结构来解释.
结论:
- p300 HAT结构为其功能和机制提供了前所未有的洞察力.
- 这项工作阐明了p300/CBP独特的催化策略和基质相互作用.
- 这些发现有助于针对p300/CBP相关疾病开发有针对性的表观遗传疗法.
相关概念视频
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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.
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02:04Co-activators and Co-repressors
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