Protein-RNA interactions mediated by silvestrol-insight into a unique molecular clamp.

IF 16.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sai Kiran Naineni, Garvit Bhatt, Ekkanat Jiramongkolsiri, Francis Robert, Regina Cencic, Sidong Huang, Bhushan Nagar, Jerry Pelletier
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引用次数: 0

Abstract

Molecular staples or interfacial inhibitors are small molecules that exert their activity through co-association with macromolecules leading to various effects on target functions. Some molecules inhibit target activity, while others generate gain-of-function complexes. We and others have previously identified two structurally distinct classes of molecular staples, pateamine A and rocaglates. These molecules inhibit eukaryotic initiation factor (eIF) 4A, a critical RNA helicase required for translation initiation, by simultaneously interacting with both RNA and protein components. Structural insights from members of these two families indicate that they wedge themselves between RNA bases during engagement. To extend our understanding of rocaglates, we investigated the RNA-binding properties of silvestrol, a natural rocaglate distinguished by the presence of a unique dioxanyloxy ring. Our study demonstrates that silvestrol expands the RNA-binding repertoire of rocaglates due to this structural characteristic, providing a rationale for improving synthetic molecular staples targeting eIF4A.

硅vestrol 介导的蛋白质-RNA 相互作用--洞察独特的分子钳。
分子钉或界面抑制剂是通过与大分子共同结合而发挥其活性的小分子,会对目标功能产生各种影响。一些分子会抑制靶标活性,而另一些则会产生功能增益复合物。我们和其他研究人员之前已经发现了两类结构不同的分子主链,即儿茶酚胺 A 和rocaglates。这些分子通过同时与 RNA 和蛋白质成分相互作用,抑制真核生物起始因子(eIF)4A(一种翻译起始所需的关键 RNA 螺旋酶)。对这两个家族成员的结构研究表明,它们在参与过程中将自己楔入 RNA 碱基之间。为了扩展我们对洛卡酯类化合物的了解,我们研究了硅vestrol 的 RNA 结合特性,硅vestrol 是一种天然洛卡酯类化合物,因含有独特的二氧环而与众不同。我们的研究表明,由于这种结构特征,硅vestrol 扩大了洛克烷酸酯的 RNA 结合范围,为改进靶向 eIF4A 的合成分子主链提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nucleic Acids Research
Nucleic Acids Research 生物-生化与分子生物学
CiteScore
27.10
自引率
4.70%
发文量
1057
审稿时长
2 months
期刊介绍: Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.
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