Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2020-05-27 , DOI: 10.1016/j.bbrc.2020.05.142 XinPeng Chen 1 , ZhaoMin Lin 2 , Le Su 3 , XiaoLing Cui 3 , BaoXiang Zhao 4 , JunYing Miao 5
Despite significant process in ubiquitin modification by using traditional genetic methods, chemical small molecules that directly target and modify ubiquitin are little reported. Here, we find that a fluorescigenic pyrazoline derivative (FPD5) could do so effectively. Molecule docking revealed that lysine 11 of ubiquitin was the key contact residue. FPD5, with stronger fluorescence, elevated the ubiquitination of beclin 1 (BECN1) and promoted autophagy. This study highlights that targeting ubiquitin by chemical small molecules enables us to modulate ubiquitination and the downstream signaling in the ubiquitin system.
中文翻译:
发现了针对泛素的发荧光吡唑啉衍生物。
尽管通过使用传统遗传方法在遍在蛋白修饰上进行了重要的过程,但直接靶向和修饰遍在蛋白的化学小分子的报道却很少。在这里,我们发现一种荧光性吡唑啉衍生物(FPD5)可以有效地做到这一点。分子对接揭示了泛素的赖氨酸11是关键的接触残基。FPD5具有更强的荧光性,增加了Beclin 1(BECN1)的泛素化并促进了自噬。这项研究强调,通过化学小分子靶向泛素可以使我们调节泛素和泛素系统中的下游信号传导。