Darya O Koshkina, Natalya V Maluchenko, Anna N Korovina, Angelina A Lobanova, Alexey V Feofanov, Vasily M Studitsky
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引用次数: 0
摘要
天然多酚白藜芦醇是一种生物活性化合物,能与 DNA 相互作用并影响某些核酶的活性。本研究采用 Western 印迹法、分光光度法、电泳迁移测定法和单颗粒佛尔斯特共振能量转移显微镜法研究了白藜芦醇对核小体和聚(ADP-核糖)聚合酶-1(PARP1)之间的相互作用以及对 PARP1 催化活性的影响。在微摩尔和亚微摩尔浓度下,白藜芦醇可抑制 PARP1 的活性,但由于多酚的聚集作用,浓度越高,抑制作用越弱。白藜芦醇对 PARP1 的抑制作用伴随着白藜芦醇与酶催化中心的结合以及 PARP1 与核糖体 DNA 亲和力的降低。在白藜芦醇存在的情况下,talazoparib与PARP1的底物结合袋同时结合,恢复了PARP1与核小体的相互作用,这表明白藜芦醇和talazoparib的结合位点是重叠的。这些数据表明,白藜芦醇可被归类为 PARP1 的天然抑制剂。
Resveratrol Inhibits Nucleosome Binding and Catalytic Activity of PARP1.
The natural polyphenol resveratrol is a biologically active compound that interacts with DNA and affects the activity of some nuclear enzymes. Its effect on the interaction between nucleosomes and poly(ADP-ribose) polymerase-1 (PARP1) and on the catalytic activity of PARP1 was studied using Western blotting, spectrophotometry, electrophoretic mobility shift assay, and single particle Förster resonance energy transfer microscopy. Resveratrol inhibited PARP1 activity at micro- and sub-micromolar concentrations, but the inhibitory effect decreased at higher concentrations due to the aggregation of the polyphenol. The inhibition of PARP1 by resveratrol was accompanied by its binding to the enzyme catalytic center and a subsequent decrease in PARP1 affinity to nucleosomal DNA. Concurrent binding of talazoparib to the substrate binding pocket of PARP1, which occurs in the presence of resveratrol, restores the interaction of PARP1 with nucleosomes, suggesting that the binding sites of resveratrol and talazoparib overlap. The data suggest that resveratrol can be classified as a natural inhibitor of PARP1.
BiomoleculesBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍:
Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.