DMSO可能会影响病毒制剂中的联体结合,体稳定性和RNA相互作用
Jiri Wald1,2,3, Nikolaus Goessweiner-Mohr4, Antonio Real-Hohn5
1Institute of Microbial and Molecular Sciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. jiri.wald@cssb-hamburg.de.
Scientific reports
|December 5, 2024
概括
甲基二硫氧化物 (DMSO) 改变RV-A89结构,导致口袋崩和RNA释放. 这种溶剂效应通过改变蛋白质和RNA相互作用,影响抗病毒药物研究.
科学领域:
- 结构生物学是结构生物学.
- 病毒学 病毒学
- 药物发现 药物发现
背景情况:
- 甲基二硫氧化物 (DMSO) 是药物研究中常见的溶剂.
- 即使在低度下,DMSO也可能导致蛋白质和RNA的结构变化.
- 抗病毒药物OBR-5-340显示对犀牛病毒菌株的差异性活性 (RV-B5与RV-A89对比).
研究的目的:
- 研究DMSO对Rhinovirus-A89 (RV-A89) 结构的影响.
- 阐明OBR-5-340对犀牛病毒菌株的差异性活性背后的机制.
- 了解DMSO如何影响RV-A89疏水口袋和RNA-蛋白相互作用.
主要方法:
- 高分辨率冷电子显微镜 (cryo-EM) 的RV-A89.
- 在平面缓冲液中对RV-A89进行结构分析,与含有DMSO的溶液相比.
- 用DMSO和没有DMSO的RV-A89结构进行比较,以确定结构变化.
主要成果:
- 在缓冲器中对RV-A89的冷EM重建显示了myristate占据了口袋因子结合部位.
- 观察到RV-A89的疏水口袋在DMSO的存在下崩.
- 缺少DMSO消除了蛋白质-RNA接口的局部异质性,表明没有口袋因素的囊灵活性增加.
结论:
- DMSO从RV-A89中出口袋因子 (myristate),导致疏水口袋崩.
- 在RNA-蛋白界面上的DMSO诱导的囊灵活性和亲和力修饰的变化可能会促进定向RNA基因组释放.
- 了解DMSO的结构影响对于解释犀牛病毒研究中的抗病毒药物疗效至关重要.
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