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概述蛋白质氨酸甲基转移酶调节剂的发展:取得的成就和未来的方向
Chao Tong1, Xiujin Chang1, Fangui Qu1
1Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China.
European journal of medicinal chemistry
|February 15, 2024
概括
蛋白质氨酸甲基转移酶 (PRMT) 调节细胞循环和DNA修复. 本综述涵盖了PRMT结构,功能和抑制剂,有助于未来的药物设计与PRMT失调相关的疾病.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 蛋白质甲基化是涉及表观遗传调节的关键翻译后修饰 (PTM).
- 基因组蛋白和非基因组蛋白甲基化会影响转录,DNA修复和细胞周期控制等关键细胞过程.
- 通过PRMTs调解的蛋白质阿基宁甲基化对于细胞循环调节和DNA修复至关重要,其失调与各种疾病有关.
研究的目的:
- 为提供蛋白质氨酸甲基转移酶 (PRMT) 的全面概述.
- 详细说明PRMTs的结构,生化功能和相关的生物活性测定.
- 审查当前PRMT抑制剂的结构功能关系,并为未来药物开发提供信息.
主要方法:
- 关于蛋白质甲基化,PRMT及其抑制剂的文献综述.
- 对PRMT的结构和功能数据的分析.
- 对已知PRMT抑制剂的结构-活性关系的检查.
主要成果:
- PRMTs是基本细胞过程的关键调节者.
- 功能障碍的PRMT与各种病理状况有关.
- 几种PRMT抑制剂正在临床研究中,证明了治疗潜力.
结论:
- 在疾病治疗中,PRMTs是治疗干预的重要目标.
- 了解PRMT的结构功能是开发有效抑制剂的关键.
- 本综述提供了指导新型PRMT向药物的设计和开发的见解.
相关概念视频
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Phase II Reactions: Methylation Reactions
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...

