通过Pyrrole-Imidazole聚胺结合诱导的DNA双重动态的长距离学调制
Sophie E T Kendall-Price1, Ryan J O Nichol2, Andrea Taladriz-Sender2
1Department of Chemistry and York Biomedical Research Institute, University of York, Heslington, York YO10 5DD, U.K.
The journal of physical chemistry letters
|July 28, 2025
概括
小沟结合配体抑制双链DNA (dsDNA) 的结构动力学,影响到30个基对外的末端脱. 这揭示了DNA识别如何影响分子行为和合成转录因子设计.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 化学生物学 化学生物学
背景情况:
- 小沟结合配体与双链DNA (dsDNA) 相互作用.
- 了解DNA结构动态对于分子识别至关重要.
- 体调制描述了在一个地点的结合如何影响远处的地点.
研究的目的:
- 为了研究小沟结合对dSDNA结构动态的全质效应.
- 量化这些动态调节的距离.
- 为了告知合成转录因子的设计.
主要方法:
- 使用时间分辨率温度跳跃红外光谱学.
- role-imidazole聚胺被用作小沟结合配体.
- 分析了短的dsDNA序列 (8-14个基对).
主要成果:
- 带结合明显抑制了dsDNA的结构动力学,包括末端磨损.
- 这种抑制从结合部位的3'和5'方向观察到.
- 确定了30个基对的传播长度,用于动态调制.
结论:
- 微小的沟结合会诱导dSDNA动态的长距离全调节.
- 这一发现增强了对DNA识别机制的理解.
- 结果为设计新型合成转录因子提供了洞察力.
相关概念视频
Ligand Binding and Linkage
4.9K
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...
4.9K
Allosteric Proteins-ATCase
5.9K
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...
5.9K
Cooperative Allosteric Transitions
2.4K
2.4K
Cooperative Binding of Transcription Regulators
6.6K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.6K
Basicity of Heterocyclic Aromatic Amines
6.3K
Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
6.3K


