泰尔米沙坦与人体素S- 甲基转移酶之间的结合力学和相互作用的机制见解
Archana Vakkayil1, Deepthi Jose2, Tom Skaria1
1Department of Bioscience and Engineering, National Institute of Technology Calicut, Calicut, Kerala, India.
Journal of pharmaceutical sciences
|August 30, 2025
概括
泰尔米萨坦药物可能与氨酸S- 甲基转移酶 (TPMT) 发生危险的相互作用,该酶对免疫抑制剂的处理至关重要. 这种相互作用可能会导致服用这两种药物的患者出现严重并发症.
科学领域:
- 生物化学
- 药理学
- 药物新陈代谢
背景情况:
- 氨酸S-甲基转移酶 (TPMT) 对于在自身免疫性疾病和移植排斥中使用的氨酸药物来说至关重要.
- 减少TPMT活动可能导致严重的骨髓抑制和死亡,促使FDA推进行基因检测.
- 泰尔米萨坦是一种广泛使用的抗高血压药物.
研究的目的:
- 研究人类TPMT与抗高血压药物telmisartan之间潜在的非目标相互作用.
- 阐明这种相互作用背后的分子机制.
主要方法:
- 使用全面的分子建模来模拟telmisartan和TPMT之间的相互作用.
- 结合模式,活性部位适应和相互作用亲缘关系的分析.
主要成果:
- 分子建模显示telmisartan以类似双基质的方式与TPMT活性部位结合.
- 这种结合阻塞了辅助因子和氨酸基质的部位.
- 与其天然辅助因子相比,特尔米萨坦对TPMT的结合亲和力更强.
结论:
- 泰尔米萨坦可以与TPMT相互作用,可能抑制其酶活性.
- 这种相互作用代表了以前未知的机制,对telmisartan和thiopurine药物的同时使用有影响.
- 需要进一步的研究来评估在服用氨酸免疫抑制剂的患者中特尔米萨坦与TPMT相互作用的临床意义.
相关概念视频
Protein-Drug Binding: Mechanism and Kinetics
924
Protein-drug binding refers to the interaction between drugs and proteins within the body. This binding process can occur intracellularly, involving drug interactions with enzymes or receptors within cells, or extracellularly, involving plasma proteins in the blood.
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
924
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
Telomeres and Telomerase
24.0K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
24.0K
ATP Synthase: Mechanism
15.1K
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...
15.1K
Factors Affecting Protein-Drug Binding: Drug Interactions
272
Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
272


