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甘草次酸(glycyrrhetinic acid,GA)是甘草主要活性组分,可诱导肿瘤细胞凋亡,抑制肿瘤细胞生长.然而,其对BLM解旋酶的抑制作用尚未见报道.本文注视甘草次酸对BLM解旋酶构象、二级结构和生化活性的影响.圆二色光谱和紫外光谱分析显示,GA可破坏BLM642-1290解旋酶α-螺旋结构,改变其构象,并具有2个结合位点.采用荧光偏振技术和自由磷检测证明,GA以浓度依赖的方式抑制BLM642-1290解旋酶与底物dsDNA及ssDNA的结合,抑制BLM642-1290解旋酶活性及ATP酶活性,且抑制类型为混合抑制.综上所述,本文证明GA可通过结合BLM解旋酶,改变BLM解旋酶构象,抑制BLM解旋酶与DNA的结合,从而抑制BLM解旋酶的生化活性.我们的发现将对深入认识GA的抗肿瘤作用有新的启示.
Glycyrrhetinic acid (GA) is the main active component of Glycyrrhiza uralensis, which can induce the apoptosis of tumor cells and inhibit the growth of tumor cells. However, the inhibition of BLM helicase has not been reported.In this paper, glycyrrhetinic acid Helicase conformation, secondary structure and biochemical activity.Cyclic dichroism and UV spectroscopy analysis showed that GA can destroy the helicase structure of BLM642-1290 helicase, change its conformation and have two binding sites. Fluorescence polarization assay and free phosphorus assay demonstrated that GA inhibited the binding of BLM642-1290 helicase to substrate dsDNA and ssDNA in a concentration-dependent manner, inhibited the BLM642-1290 helicase activity and ATPase activity, and the inhibition type was mixed In conclusion, GA has been shown to inhibit the biochemical activity of BLM helicase by binding to the BLM helicase, altering the conformation of BLM helicase, inhibiting the binding of BLM helicase to DNA, In-depth understanding of the antitumor effect of GA has a new revelation.