从活性位变异和维培林类酶中的β-8环相互作用中获得的结构洞察力
Jake C Lachowicz1, Steven Grudman2, Jeffrey B Bonanno1
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Structure (London, England : 1993)
|May 15, 2025
概括
具有特定动机 (NΦF) 的类似维培林的酶 (VLEs) 可能会使用CTP. 工程β-8循环可以切换VLE基质选择性,提供创建替代核三酸盐的新方法.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 结构生物学 结构生物学
背景情况:
- 维佩林和类似维佩林的酶 (VLEs) 是激进的SAM酶,可催化核三酸盐的脱水.
- VLE表现出取决于物种的基质选择性,一些真菌VLE具有明显的NΦF动机.
研究的目的:
- 为了研究NΦF VLEs的基质特异性.
- 了解VLE中基质选择性的结构决定因素.
- 为改变基质偏好设计VLE.
主要方法:
- 生物信息学分析
- 酶性检测试验 酶性检测试验
- 在X射线晶体学.
- 蛋白质工程是一种蛋白质工程.
主要成果:
- NΦF VLE被确定为可能使用CTP的酶.
- 通过将TvVip1的β-8循环与来自CTP选择性viperin的循环进行工程,成功地将基质选择性从UTP切换到CTP.
- 获得了关于VLE基质选择性的结构见解.
结论:
- β-8循环是VLE中基质选择性的关键决定因素.
- 工程VLEs提供了一个生产替代3ahydro-3ahydro,4ahydro-didehydronucleoside三酸盐 (ddhNTPs) 的潜在策略.
相关概念视频
Ligand Binding and Linkage
4.7K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.7K
Enzymes
80.2K
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...
80.2K
Allosteric Proteins-ATCase
5.6K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.6K
Conserved Binding Sites
4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K
Induced-fit Model
79.9K
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...
79.9K
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


