人类碳酸无水酶IX的糖基化催化域的分子建模
Ritwika Dey1, Srabani Taraphder1
1Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
The journal of physical chemistry. B
|November 2, 2024
概括
这项研究揭示了人类碳酸无水酶IX (HCA IX) 上的糖链如何采用各种形状. 研究人员确定了特定的蛋白质残留物,这些残留物影响了在催化部位附近罕见的糖甘背折叠事件.
科学领域:
- 生物化学和分子生物学
- 结构生物学 结构生物学
- 计算化学计算化学
背景情况:
- 由于糖结合的灵活性和结合,甘氨酸具有显著的结构多样性.
- 了解甘氨酸构造对于它们的生物功能至关重要,特别是当它们与像人类碳酸无水酶IX (HCA IX) 这样的蛋白质相连时.
研究的目的:
- 为了研究与HCA IX (HCA IX-c) 催化域相连的N-链 glycans 的构造格局.
- 为了确定相对于蛋白质表面和指导这些构造的氨基酸残留的糖方向.
- 描述甘氨酸形状转换的动态和动力学.
主要方法:
- 进行了广泛的分子动力学 (MD) 模拟 (30 μs) 和加速的MD模拟 (2 μs).
- 利用两个不同的力场来建模糖链和HCA IX波动.
- 应用隐藏的马尔科夫状态建模来分析自由能量概况和动力学.
主要成果:
- 确定了几种稳定的甘氨酸方向,远离蛋白质表面,具有快速的相互转换率 (10^7-10^10 s^-1).
- 发现了一种罕见的甘氨酸构造,它向蛋白质表面折叠,接近具有催化作用的重要残留物Glu-106.
- 编目特定的蛋白质残留物参与促进这些罕见的糖甘反折事件.
结论:
- 这项研究阐明了HCA IX上的甘氨酸的动态构造行为.
- 特定的蛋白质-甘氨酸相互作用决定了甘氨酸的定位,包括对潜在的全调节或酶活性调节至关重要的罕见事件.
- 计算建模提供了对蛋白质结构和糖基化之间的复杂相互作用的见解.
相关概念视频
Molecular Models
38.0K
Physical models representing molecular architectures of chemical compounds play essential roles in understanding chemistry. The use of molecular models makes it easier to visualize the structures and shapes of atoms and molecules.
38.0K
Fischer Projections
13.1K
Learning to draw Fischer projections of molecules and understanding their relevance plays a crucial role in the visual depiction of organic molecules. A Fischer projection is a two-dimensional projection on a planar surface to simplify the three-dimensional wedge–dash representation of molecules. This is especially helpful in the case of molecules with multiple chiral centers that can be difficult to draw. Here, all the bonds of interest are represented as horizontal or vertical lines.
13.1K
Globular and Fibrous Proteins
43.4K
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
43.4K
Gene Families
8.8K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
8.8K
Molecular Structure and Acidity
16.9K
An acid can be deprotonated to form a conjugate base or an anion. If the produced anion is more stable, then the acid is stronger. On the contrary, if the anion is unstable, then the acid is weaker. Hence, to determine the acidity of the compound, the stability of its conjugate base is studied using various factors.
The size effect explains the change in atomic size on acidity. When comparing the acids formed from elements that belong to the same column in the periodic table, their atomic sizes...
The size effect explains the change in atomic size on acidity. When comparing the acids formed from elements that belong to the same column in the periodic table, their atomic sizes...
16.9K
Aldehydes and Ketones with Water: Hydrate Formation
3.1K
An oxygen-based nucleophile, like water, can undergo addition reactions with aldehydes and ketones. The reaction leads to the formation of hydrates, also referred to as 1,1-diols or geminal diols.
The formation of hydrates is a reversible reaction. Hydrate formation is influenced by steric and electronic factors accompanying the alkyl substituents on the carbonyl group: The rate of hydrate formation increases with a decrease in the number of alkyl groups attached to the carbonyl carbon. Hence,...
The formation of hydrates is a reversible reaction. Hydrate formation is influenced by steric and electronic factors accompanying the alkyl substituents on the carbonyl group: The rate of hydrate formation increases with a decrease in the number of alkyl groups attached to the carbonyl carbon. Hence,...
3.1K


