从分子模拟中获得植物芳香氨基酸脱碳酶的活性场所氧气可及性和催化环动力学
Yitao Gou1, Tianjie Li1, Yi Wang1
1Department of Physics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Biochemistry
|July 15, 2024
概括
植物酶称为芳香氨基酸脱碳酶 (AAADs) 可以执行不同的反应. 一个单一的突变改变了它们的功能,影响了氧气获取和催化机制,揭示了对酶进化的洞察力.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 植物科学 植物科学
背景情况:
- 芳香氨基酸脱碳酶 (AAADs) 是一种依赖于酸-5'-酸盐 (PLP) 的酶. 植物AAAD表现出各种功能,包括正规脱碳和氧化脱胺 (芳香性乙甲合成酶,AAS). 催化循环中的单个氨酸-氨酸突变可以切换酶功能.
研究的目的:
- 研究植物酶中正规AAAD和AAS活动之间的功能切换.
- 阐明氨酸-氨酸突变对酶机制的影响,特别是氧气可获得性.
- 探索催化循环动态在植物AAAD家族功能的作用.
主要方法:
- 对Papaver somniferum l-tyrosine decarboxylase (PsTyDC) 和其Y350F突变体的隐性带采样 (ILS) 计算.
- 分析3D O2自由能量概况,以评估氧气的可访问性.
- 在Catharanthus roseus的分子动力学 (MD) 模拟中使用l-三脱氧酶 (CrTDC) 来研究催化循环的动力学.
主要成果:
- ILS的计算揭示了野生类型PsTyDC及其Y350F突变体的O2自由能量特征,表明氧气可获得性发生了变化.
- Y350F突变影响了该酶进行氧化除的能力.
- MD模拟突出了CRTDC中催化循环的动态性质,这对于AAAD功能至关重要.
结论:
- 氨酸-氨酸突变显著影响了植物AAAD的催化机制和基质加工.
- 酶的结构元素,特别是催化循环,以及它们的结构动态是植物AAAD家族内功能多样性的关键决定因素.
- 像ILS和MD这样的计算方法对于理解酶机制和进化有价值.
相关概念视频
Allosteric Proteins-ATCase
5.7K
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...
5.7K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Ligand Binding and Linkage
4.8K
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...
4.8K
The Calvin Benson Cycle
4.5K
Ribulose 1,5- bisphosphate carboxylase/oxygenase (RuBisCo) is a critical enzyme that catalyzes carbon dioxide assimilation during photosynthesis. However, it is an inefficient enzyme, having an extremely slow catalytic rate. A typical enzyme can process about a thousand molecules per second; however, RuBisCo fixes only around three-carbon dioxides per second. Photosynthetic cells compensate for this slow rate by synthesizing very high amounts of RuBisCo, making it the most abundant single...
4.5K
Aromatic Hydrocarbon Anions: Structural Overview
2.8K
Neutral hydrocarbons like cyclopentadiene with an odd number of carbon atoms and one intervening CH2 group in the ring are not aromatic. Cyclopentadiene with 4 π electrons does not satisfy the 4n + 2 π electron rule. Additionally, the intervening CH2 group is sp3 hybridized and lacks a vacant p orbital, thereby interrupting the overlap of p orbitals in a continuous manner and preventing the delocalization of π electrons throughout the ring.
Due to the absence of continuous...
Due to the absence of continuous...
2.8K
Aromatic Hydrocarbon Cations: Structural Overview
2.8K
Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group...
Removing one hydrogen from the intervening CH2 group...
2.8K


