丁丁氨酸减小酶 (PAD):在治疗慢性疾病方面是一个有前途的目标
Pegah Mansouri1, Pardis Mansouri1, Esmaeil Behmard2
1Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran.
International journal of biological macromolecules
|August 10, 2024
概括
丁氨酸减小酶 (PAD) 酶修改蛋白质,导致诸如类风湿性关节炎等疾病. 目前的抑制剂显示出有前途,但针对性治疗需要更多的研究.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 免疫学 免疫学 免疫学
背景情况:
- 1958年,在蛋白质中发现了转化后修饰的素化,这是一种后翻译性修饰.
- 丁氨酸减小酶 (PAD) 酶催化氨酸转化为氨酸.
- PAD酶失调与炎症性疾病和癌症有关.
研究的目的:
- 审查PAD酶,特别是PAD2和PAD4在类风湿性关节炎 (RA) 发病过程中的作用.
- 讨论PAD酶的结构方面,包括结合位和活性位的组成.
- 总结现有的泛PAD和选择性PAD抑制剂,并强调未来的研究方向.
主要方法:
- 关于PAD酶功能的文献综述,疾病相关性和抑制剂的发展.
- 对PAD酶结构的结晶学数据的分析.
- 将PAD抑制剂分类为泛PAD和异型选择性药物.
主要成果:
- 通过产生素自抗原和炎症性细胞因子,PAD2和PAD4有助于RA.
- PAD4与中性粒细胞外细胞陷 (NET) 的形成和血栓形成有关.
- 现有的抑制剂包括泛PAD药物 (例如,F-阿米丁) 和选择性抑制剂 (例如,AFM-30a用于PAD2,JBI589用于PAD4).
结论:
- PAD酶在RA和其他疾病的发病过程中至关重要.
- 需要对当前PAD抑制剂进行进一步评估.
- 新型,高特异性的PAD异型抑制剂的开发是未来的一个关键目标.
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