短链伊诺伊尔-CoA水合酶 (ECHS1) 基质识别的结构和生化机制
Gengchen Su1,2, Youwei Xu3, Binxian Chen2
1Department of Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, 100730, Beijing, China.
Communications biology
|April 16, 2025
概括
短链伊诺伊尔-CoA酸酶 (ECHS1) 缺乏影响脂肪酸代谢,并导致心肌病. 结构研究揭示了ECHS1如何识别基质,提供了对疾病机制的见解.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 分子代谢的分子代谢.
背景情况:
- 短链伊诺伊尔-CoA酸酶 (ECHS1) 对于线粒体脂肪酸β-氧化至关重要.
- 缺乏ECHS1与疾病有关,尤其是心肌病.
- 对于ECHS1基质识别的精确机制尚不清楚.
研究的目的:
- 阐明ECHS1基质识别的结构和生化机制.
- 研究突变对ECHS1功能和基质结合的影响.
- 为了解ECHS1缺陷相关疾病提供结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定高分辨率结构.
- 解决了apo-ECHS1的结构和与各种乙烯基-CoAs复合物的结构.
- 进行了生物化学测试,以评估酶活性和结合亲和力.
主要成果:
- 确定了ECHS1的基结构.
- 结构揭示了不同长度的乙-CoA链的不同基质识别机制.
- 与疾病相关的和关键点突变显著改变了基质结合和酶活性.
结论:
- ECHS1基质的识别取决于-CoA链的长度.
- 突变影响ECHS1的功能,提供了对疾病发病的洞察力.
- 结构和生化数据为研究ECHS1缺陷和相关心肌病症提供了基础.
相关概念视频
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
8.2K
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
8.2K
Introduction to Mechanisms of Enzyme Catalysis
7.8K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
7.8K
Alkynes to Aldehydes and Ketones: Acid-Catalyzed Hydration
8.1K
Introduction
Analogous to alkenes, alkynes also undergo acid-catalyzed hydration. While the addition of water to an alkene gives an alcohol, hydration of alkynes produces different products such as aldehydes and ketones.
Analogous to alkenes, alkynes also undergo acid-catalyzed hydration. While the addition of water to an alkene gives an alcohol, hydration of alkynes produces different products such as aldehydes and ketones.
8.1K
Induced-fit Model
79.8K
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...
79.8K
Enzymes
80.1K
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...
80.1K
Regioselective Formation of Enolates
2.5K
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
2.5K


