阐明因口疫病毒3C蛋白酶活性位点突变引起的结构动态
Sthitaprajna Sahoo1, Hak-Kyo Lee1,2, Donghyun Shin1
1Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju, Republic of Korea.
PloS one
|April 21, 2025
概括
使用分子动力学研究了口病病毒3C蛋白酶 (3Cpro) 突变C142S和C142L. C142S突变显示出显著的结构变化,影响了酶活性,并为新型抗病毒疗法提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 病毒学 病毒学
背景情况:
- 口疫病毒 (FMDV) 的复制依赖于3C蛋白酶 (3Cpro) 来处理聚蛋白质.
- 3Cpro是开发FMDV治疗方法的关键目标.
- 保存的β-带区域和活性部位残留物C142对于3Cpro功能至关重要.
研究的目的:
- 调查FMDV 3Cpro活点突变体 (C142S和C142L) 的内在动态和构造变化.
- 阐明这些突变如何影响3Cpro的结构和功能,有助于设计新的抑制剂.
主要方法:
- 对野生型 (WT) 3Cpro及其C142S和C142L突变物进行了多重复制的分子动力学 (MD) 模拟.
- 分析包括基本动态,交叉相关性和残留物相互作用网络 (中间中心性).
主要成果:
- 与WT和C142L相比,C142S突变体表现出实质性的结构转变,并改变了基本的动态.
- C142L显示了与WT相似的残留抗相关性模式,表明了不同的功能影响.
- 在WT和突变3Cpro.中确定了信号传播途径.
结论:
- C142S突变可能通过诱导形状变化来抑制3Cpro活性,从而使β-丝带区域向催化口袋倾斜.
- C142L的替代可能会通过改变β-带形状来影响基质结合.
- 了解这些动态行为有助于开发有效的口病抑制剂.
更多相关视频
07:53A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
33.1K
08:40Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
Published on: March 1, 2019
58.8K
相关概念视频
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
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
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
Viral Mutations
32.0K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.0K
Viral Structure
61.0K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
61.0K
Mechanical Protein Function
2.0K
2.0K
