Effects of tetrandrine derivative HL-49 on biological property of Bloom DNA helicase
10.3969/j.issn.1001-1978.2022.02.011
- Author:
Jin-He LIU
1
;
Tian XIANG
1
;
Wei LUO
1
;
Kai-Lin YANG
1
;
Wang-Ming ZHANG
2
;
Jie-Lin LIU
2
;
Wen-Tao YAN
3
;
Ze-Quan XU
4
Author Information
1. Natl. and Guizhou Jt. Eng. Ixib for Cell Eng. and Biomed. Tech. .Ctr. for Tissue Eng. and Stem Cell Res., Guizhou Medical University .Guiyang, Guizhou Province Key Ixib for Regenerative Medicine
2. College of Basic Medicine, Guizhou Medical University, Dept of Immunology
3. First Affiliated Hospital of Guizhou University of Chinese Medicine .
4. School of Clinical Laboratory Medicine, Guizhou Medical University .
- Publication Type:Journal Article
- Keywords:
ATPase activity;
biochemical properties;
BLM helicase;
conformation;
fluorescence polarization;
tetrandrine derivative
- From:
Chinese Pharmacological Bulletin
2022;38(2):209-214
- CountryChina
- Language:Chinese
-
Abstract:
Aim To study the effect of tetrandrine derivative HL-49 on the conformation and biological ac-tivity of Bloom helicase ( BLM ) , and to explore its antitumor mechanism.Methods The effect of HL-49 on the conformation of BLM helicase was studied by ultra- violet spectroscopy.The effects of HL-49 on DNA binding activity, DNA chain dissociation activity and ATPase activity of HL-49 on BLM DNA helicase were analyzed by fluorescence polarization and malachite green-ammonium phosphomolybdate colorimetric method.Results HL-49, a tetrandrine derivative, indirectly inhibited the ATPase activity of BLM DNA heli- case and DNA unwinding activity by reversible binding with DNA.The results of fluorescence polarization experiments showed that HL-49 could not affect the bind ing activity of BLM DNA helicase to DNA (dsDNA/ss- DNA) , but could bind to DNA in a concentration-de- pendent manner (P < 0.01).With the increase of HL- 49 concentration, the DNA unwinding ability of BLM DNA helicase decreased, and the Kobs value decreased gradually.The results of malachite green-ammonium phosphomolybdate colorimetry showed that HL-49 could significantly inhibit the ATPase activity of BLM DNA helicase.Conclusions HL49 can inhibit the ATPase activity and DNA unwinding activity of BLM DNA helicase by the reversible binding with DNA.
