关于双醇与PPARγ的结合方式的结构研究
Abibe Useini1, Inken Kaja Schwerin2, Georg Künze2,3,4
1Institute of Bioanalytical Chemistry, Centre for Biotechnology and Biomedicine, Leipzig University, Deutscher Platz 5, 04103 Leipzig, Germany.
Biomolecules
|June 27, 2024
概括
双A (BPA) 和双B (BPB) 结合PPARγ联体结合域,但没有激活它. 分子动力学模拟揭示了影响它们结合模式的关键相互作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 双A (BPA) 和双B (BPB) 是常见的塑料添加剂,具有潜在的内分泌干扰和代谢健康影响.
- 过氧体增殖器激活受体玛 (PPARγ) 对于代谢调节和脂肪生成至关重要,使其成为了解肥胖症的关键目标.
研究的目的:
- 使用结构和模拟方法研究PPARγ和BPA/BPB之间的分子相互作用.
- 阐明BPA和BPB与PPARγ结合的结合机制和潜在的功能后果.
主要方法:
- 使用X射线结晶学来确定PPARγ联体结合域内BPA和BPB的结合位.
- 用分子动力学 (MD) 模拟和自由能量分析来研究动态相互作用和能量贡献.
主要成果:
- 结晶学证实BPA和BPB与PPARγ在C285附近结合,这是一个已知与其他PPARγ调节器相互作用的地点.
- 在激活函数2位点中,BPA和BPB与Y437没有相互作用,这表明它们无法稳定活性PPARγ结构.
- MD模拟确定I341对BPA和BPB的结合有显著的能量贡献.
结论:
- BPA和BPB与PPARγ结合,但由于无法稳定活性构造,不太可能激活其信号通路.
- 结合相互作用,特别是涉及I341的结合相互作用,为BPA和BPB与PPARγ的相互作用的分子基础提供了洞察力.
相关概念视频
02:18The Equilibrium Binding Constant and Binding Strength
12.9K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
12.9K
00:49Ligand 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
01:31Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
02:13Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
39
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
39
01:24π Molecular Orbitals of 1,3-Butadiene
8.8K
Conjugated dienes have lower heats of hydrogenation than cumulated and isolated dienes, making them more stable. The enhanced stabilization of conjugated systems can be understood from their π molecular orbitals.
The simplest conjugated diene is 1,3-butadiene: a four-carbon system where each carbon is sp2-hybridized and has an unhybridized p orbital that contains an unpaired electron. According to molecular orbital theory, atomic orbitals combine to form molecular orbitals such that the number...
The simplest conjugated diene is 1,3-butadiene: a four-carbon system where each carbon is sp2-hybridized and has an unhybridized p orbital that contains an unpaired electron. According to molecular orbital theory, atomic orbitals combine to form molecular orbitals such that the number...
8.8K