一个前酶的小分子激活剂
Dennis W Wolan1, Julie A Zorn, Daniel C Gray
1Department of Pharmaceutical Chemistry, University of California, San Francisco, Byers Hall, 1700 4th Street, San Francisco, CA 94158, USA.
概括
研究人员发现了第一个直接激活益酶的小分子,特别是apoptotic procaspases-3和-6. 这些新型激活剂绕过正常信号传递,迅速诱导细胞亡,并提供对细胞过程的新控制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 大多数人体蛋白酶存在于非活跃的益酶中,需要严格的监管.
- 益酶激活是许多生物过程中的关键步骤,包括亡和分化.
研究的目的:
- 确定和描述第一个能够直接激活益酶的小分子.
- 研究这些小分子激活 procaspases-3 和 -6.pases 的机制.
- 探索这些激活剂在控制细胞亡和细胞分化方面的潜力.
主要方法:
- 小分子选和表征. 小分子选和表征.
- 对前酶激活的生物化学和生物物理分析.
- 基于细胞的测试来评估亡诱导.
- 突变分析以确定抵抗机制.
主要成果:
- 识别了第一个直接激活亡性前-3和-6的小分子.
- 证明这些激活剂通过稳定特定形状来诱导自保护性激活.
- 普罗卡斯酶激活剂绕过上游信号,导致各种细胞系的快速亡.
- 鉴定对小分子激活产生抗性的突变.
结论:
- 小分子可以直接激活益酶,为生物控制提供一种新的方法.
- 这些激活剂提供了一个直接操纵子者体在亡和分化中的工具.
- 这些发现为发现其他前酶激活剂和理解它们的基本作用开辟了道路.
更多相关视频
09:42Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
08:56Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments
Published on: July 5, 2014
相关概念视频
Enzymes
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Eukaryotic Transcription Activators
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Enzymes and Activation Energy
The activation energy (or free energy of activation), abbreviated as Ea, is the small amount of energy input necessary for all chemical reactions to occur. During chemical reactions, certain chemical bonds break, and new ones form. For example, when a glucose molecule breaks down, bonds between the molecule's carbon atoms break. Since these are energy-storing bonds, they release energy when broken. However, the molecule must be somewhat contorted to get into a state that allows the bonds to...
Enzymes and Activation Energy
The activation energy (or free energy of activation), abbreviated as Ea, is the small amount of energy input necessary for all chemical reactions to occur. During chemical reactions, certain chemical bonds break, and new ones form. For example, when a glucose molecule breaks down, bonds between the molecule's carbon atoms break. Since these are energy-storing bonds, they release energy when broken. However, the molecule must be somewhat contorted to get into a state that allows the bonds to...
Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
