水飞蓟宾和姜黄素是抗突变囊性纤维化跨膜调节蛋白的有效配体。

IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Areeba Akram, Azra Sakhawat, Muhammad Usman Ghani, Muhammad Umer Khan, Raima Rehman, Qurban Ali, Peng Jin-Liang, Daoud Ali
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引用次数: 0

摘要

囊性纤维化跨膜调节器(CFTR)是一种重要的蛋白质,负责离子在细胞膜上的移动。囊性纤维化(CF)是由于 CFTR 基因突变产生了功能失调的 CFTR 蛋白。作为目标结构的 CFTR 蛋白序列是从 UniProt 和 PDB 数据库中获取的。配体的选择是通过虚拟筛选进行的,从 65 种配体中选出了前 3 种配体,它们分别是 Silibinins、姜黄素、去甲氧基姜黄素和参考药物 Trikafta (R*)。根据对接和 ADMET 分析,天然配体(丝利比宁和姜黄素)比其他天然化合物和参比药物(R*)显示出最佳的结合能、药动学和自由毒性。此外,还建立了 200 ns 的 MD 模拟,以确保天然配体(丝利宾和姜黄素)与目标蛋白质的良好动态结合,并保持蛋白质-配体复合物的稳定性。由此得出结论,西利宾类和姜黄素通过改善贩运和恢复原有功能,更有能力降低突变 CFTR 蛋白的影响。总之,硅烷化研究证明了西利宾素和姜黄素作为囊性纤维化治疗药物的潜力,尤其是对 D614G 突变蛋白的治疗。它们在增强 CFTR 功能的同时还能减轻细胞压力和炎症反应,再加上其良好的安全性和可及性,使它们成为囊性纤维化治疗方案的重要补充。要充分发挥它们的潜力并将其纳入有效的治疗方案,还需要进一步的实验和临床验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Silibinins and curcumin as promising ligands against mutant cystic fibrosis transmembrane regulator protein.

Silibinins and curcumin as promising ligands against mutant cystic fibrosis transmembrane regulator protein.

Cystic Fibrosis Transmembrane Regulator (CFTR) is a significant protein that is responsible for the movement of ions across cell membranes. The cystic fibrosis (CF) occur due to the mutations in the CFTR gene as it produces the dysfunctional CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands selection was performed through virtual screening and top 3 ligands choose out of 65 ligands silibinins, curcumin, demethoxycurcumin were selected with a reference drug Trikafta (R*). According to docking, ADMET analyses, the natural ligands (Silibinins and Curcumin) displayed best binding energy, pharmacokinetic and free toxicity than other natural compounds and reference drug (R*). An MD simulation for 200 ns was also established to ensure that natural ligands (Silibinins and Curcumin) attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that silibinins and curcumins have a better capacity to decrease the effect of mutant CFTR protein through improved trafficking and the restoration of original function. In conclusion, in silico studies demonstrate the potential of silibinins and curcumin as therapeutic agents for cystic fibrosis, particularly for the D614G mutated protein. Their ability to increase CFTR function while reducing cellular stress and inflammation, together with their favorable safety profile and accessibility could make them valuable additions to cystic fibrosis treatment options. Further experimental and clinical validation will be required to fully realize their potential and include them into effective therapy regimens.

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来源期刊
AMB Express
AMB Express BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
7.20
自引率
2.70%
发文量
141
审稿时长
13 weeks
期刊介绍: AMB Express is a high quality journal that brings together research in the area of Applied and Industrial Microbiology with a particular interest in ''White Biotechnology'' and ''Red Biotechnology''. The emphasis is on processes employing microorganisms, eukaryotic cell cultures or enzymes for the biosynthesis, transformation and degradation of compounds. This includes fine and bulk chemicals, polymeric compounds and enzymes or other proteins. Downstream processes are also considered. Integrated processes combining biochemical and chemical processes are also published.
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