膜内部的蛋白解是一种以速率控制的反应,不受基质亲和力驱动
Seth W Dickey1, Rosanna P Baker, Sangwoo Cho
1Howard Hughes Medical Institute, Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Room 507 PCTB, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Cell
|December 10, 2013
概括
状蛋白酶缓慢地切割膜蛋白,基质封闭,而不是亲和力,控制反应速度. 这种内膜蛋白解酶机制对疾病和药物设计有影响.
科学领域:
- 膜生物学 膜生物学
- 酶学 是一种酶学.
- 生物化学 生物化学
背景情况:
- 超膜的酶分裂释放蛋白质,控制信号通路,并与许多疾病有关.
- 脂质双层内的膜内蛋白解的机制仍然不太清楚.
研究的目的:
- 实时在膜内定量质询体蛋白解.
- 阐明膜内蛋白解的动力学和机械学特征.
主要方法:
- 开发了一种可诱导的复制系统,用于实时分析形蛋白解.
- 利用基质突变物和溶剂同位素效应来分析反应动力学.
- 研究的酶基质亲和力和催化效率 (kcat).
主要成果:
- 状蛋白酶对基质的生理亲和力很低 (Kd ~ 190 微米).
- 蛋白质分解效率的差异主要体现在kcat值,而不是亲和力.
- 基质封闭,而不是水解,被确定为速度限制的步骤.
- 单个蛋白质溶解事件在膜内发生在几分钟内.
结论:
- 体内膜蛋白解是一种缓慢的,动力控制的过程,与亲和力驱动的反应不同.
- 该机制与某些DNA修复酶有相似之处,这表明其具有更广泛的生物相关性.
- 这些发现为机理学理解和潜在的药物设计提供了洞察力,这些药物设计的目标是内蛋白酶.
相关概念视频
Protein Diffusion in the Membrane
5.1K
Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
5.1K
Enzymes
88.2K
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...
88.2K
Enzyme Kinetics
102.0K
Enzymes speed up reactions by lowering the activation energy of the reactants. The speed at which the enzyme turns reactants into products is called the rate of reaction. Several factors impact the rate of reaction, including the number of available reactants. Enzyme kinetics is the study of how an enzyme changes the rate of a reaction.
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
102.0K
Introduction to Enzyme Kinetics
28.6K
Enzyme kinetics studies the rates of biochemical reactions. Scientists monitor the reaction rates for a particular enzymatic reaction at various substrate concentrations. Additional trials with inhibitors or other molecules that affect the reaction rate may also be performed.
The experimenter can then plot the initial reaction rate or velocity (Vo) of a given trial against the substrate concentration ([S]) to obtain a graph of the reaction properties. For many enzymatic reactions involving a...
The experimenter can then plot the initial reaction rate or velocity (Vo) of a given trial against the substrate concentration ([S]) to obtain a graph of the reaction properties. For many enzymatic reactions involving a...
28.6K
Induced-fit Model
86.6K
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
86.6K
Introduction to Enzymes
29.1K
The use of enzymes by humans dates to 7000 BCE. Humans first used enzymes to ferment sugars and produce alcohol without knowing that this was an enzyme-catalyzed reaction. Wilhelm Kuhne coined the term 'enzyme' in 1877 from the Greek words ‘en’ meaning ‘in’ or ‘within’ and ‘zyme’ meaning ‘yeast.’
Most enzymes are proteins that speed up biochemical reactions without being consumed. Enzymes contain one or more active sites that...
Most enzymes are proteins that speed up biochemical reactions without being consumed. Enzymes contain one or more active sites that...
29.1K


