Department of Bioengineering, Faculty of Biology, Lomonosov Moscow State University, 12, Leninskie Gory, Moscow 119234, Russia.
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya, 16/10, Moscow 117437, Russia.
Biomolecules. 2024 Nov 2;14(11):1398. doi: 10.3390/biom14111398.
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.
天然多酚白藜芦醇是一种具有生物活性的化合物，可与 DNA 相互作用，并影响某些核酶的活性。使用 Western blot、分光光度法、电泳迁移率变动分析和单粒子Förster 共振能量转移显微镜研究了白藜芦醇对核小体和聚（ADP-核糖）聚合酶-1（PARP1）之间相互作用以及 PARP1 催化活性的影响。白藜芦醇在微摩尔和亚微摩尔浓度下抑制 PARP1 活性，但在较高浓度下，由于多酚的聚集，抑制作用减弱。白藜芦醇对 PARP1 的抑制伴随着其与酶催化中心的结合，随后 PARP1 对核小体 DNA 的亲和力降低。在白藜芦醇存在的情况下，他拉唑帕尼与 PARP1 的底物结合口袋的同时结合，恢复了 PARP1 与核小体的相互作用，表明白藜芦醇和他拉唑帕尼的结合位点重叠。数据表明，白藜芦醇可以归类为 PARP1 的天然抑制剂。
