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荧光光谱法揭示白藜芦醇与亚马逊利什曼原虫Sir2相关蛋白1(LaSir2RP1)中的疏水口袋结合。

Fluorescence Spectroscopy Reveals Resveratrol Binding to a Hydrophobic Pocket in Leishmania amazonensis Sir2-Related Protein 1 (LaSir2RP1).

作者信息

Fessel Melissa R, Povinelli Ana P R, Fontes Veronica S, Cano Maria Isabel N, Ramos Carlos H I

机构信息

Chemistry Institute, University of Campinas UNICAMP, Campinas, SP, 13083-970, Brazil.

Dept of Genetics, Microbiology and Immunology, Biosciences Institute, Universidade Estadual Paulista Júlio de Mesquita Filho, UNESP, Botucatu, SP, 18618-689, Brazil.

出版信息

Protein J. 2025 Jun 22. doi: 10.1007/s10930-025-10275-8.

DOI:10.1007/s10930-025-10275-8
PMID:40544398
Abstract

Resveratrol, a natural phytoalexin synthesized by certain plants in response to injury, exhibits antimicrobial properties and various medically significant effects, including anticancer and antiaging activities. Although its exact mechanism of action is still under investigation, it is believed to involve its interaction with a group of protein deacetylases known as sirtuins. Sirtuins are crucial in regulating metabolism, stress responses, and processes such as lifespan extension through caloric restriction. In this study, we report the inhibitory effect of resveratrol on the growth of Leishmania amazonensis promastigotes, highlighting its potential as a microbicide. Through fluorescence spectroscopy assays and in silico analysis, we identified and characterized the interaction between resveratrol and Sir2-related protein 1 from L. amazonensis (rLaSir2RP1). Our results demonstrate a direct interaction between resveratrol and rLaSir2RP1, characterized by a binding constant of 10 M. This interaction involves a single binding site located near a hydrophobic pocket, which includes its solely tryptophan residue.

摘要

白藜芦醇是某些植物在受到损伤时合成的一种天然植保素,具有抗菌特性以及多种医学上的重要作用,包括抗癌和抗衰老活性。尽管其确切作用机制仍在研究中,但据信它与一组称为沉默调节蛋白的蛋白质脱乙酰酶相互作用有关。沉默调节蛋白在调节新陈代谢、应激反应以及通过热量限制延长寿命等过程中起着关键作用。在本研究中,我们报告了白藜芦醇对亚马逊利什曼原虫前鞭毛体生长的抑制作用,突出了其作为杀微生物剂的潜力。通过荧光光谱分析和计算机模拟分析,我们鉴定并表征了白藜芦醇与来自亚马逊利什曼原虫的Sir2相关蛋白1(rLaSir2RP1)之间的相互作用。我们的结果表明白藜芦醇与rLaSir2RP1之间存在直接相互作用,其结合常数为10 M。这种相互作用涉及位于一个疏水口袋附近的单个结合位点,该口袋包含其唯一的色氨酸残基。

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