在腺酸激酶活性部位的诱导的结构重组
Kwangho Nam1, Abdul Raafik Arattu Thodika1, Sonja Tischlik2
1Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX 76019, USA.
Science advances
|August 9, 2024
概括
(Mg2+) 对于转移反应至关重要. 这项研究揭示了Mg2+如何重组腺酸酶活性位点,优化基质角度以实现高效的催化.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 转移对细胞信号传递和新陈代谢至关重要.
- 离子 (Mg2+) 作为一个重要的辅助因子,主要用于静电基板激活.
- 在酶中Mg2+的完全催化作用仍然不完全理解.
研究的目的:
- 阐明在腺酸激酶中Mg2+依赖的结构重组的分子机制.
- 调查Mg2+在优化可逆基转移活性位点中的作用.
主要方法:
- 整合结构生物学技术.
- 分子动力学 (MD) 模拟.分子动力学 (MD) 模拟.
- 遗传学分析和酶学试验.
主要成果:
- 2+诱导ATP和ADP基质在腺酸酶活性部位内的构造变化.
- 基质角度的显著30°调整优化了可逆转移的酶.
- MD模拟确定了连接基质角度波动与酶动态的构造性子状态.
结论:
- 2+通过诱导特定的结构重组,在酶催化中发挥关键作用.
- 这些发现增强了对酶中Mg2+激活机制的理解.
- 这些见解对于可逆和不可逆转移反应都很重要.
相关概念视频
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Introduction to Mechanisms of Enzyme Catalysis
8.0K
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...
8.0K
cAMP-dependent Protein Kinase Pathways
6.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.2K
ATP Synthase: Mechanism
14.3K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.3K
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
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
2.6K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
2.6K


