SARS-CoV-2 Mpro Dihedral Angles Reveal Allosteric Signaling.

IF 3.2 4区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Proteins-Structure Function and Bioinformatics Pub Date : 2025-03-03 DOI:10.1002/prot.26814

Daniel Evans, Samreen Sheraz, Albert Y Lau

引用次数: 0

Abstract

In allosteric proteins, identifying the pathways that signals take from allosteric ligand-binding sites to enzyme active sites or binding pockets and interfaces remains challenging. This avenue of research is motivated by the goals of understanding particular macromolecular systems of interest and creating general methods for their study. An especially important protein that is the subject of many investigations in allostery is the SARS-CoV-2 main protease (Mpro), which is necessary for coronaviral replication. It is both an attractive drug target and, due to intense interest in it for the development of pharmaceutical compounds, a gauge of the state of the art approaches in studying protein inhibition. Here we develop a computational method for characterizing protein allostery and use it to study Mpro. We propose a role of the protein's C-terminal tail in allosteric modulation and warn of unintuitive traps that can plague studies of the role of protein dihedral angles in transmitting allosteric signals.

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SARS-CoV-2 Mpro二面角揭示变构信号

在变构蛋白中，识别信号从变构配体结合位点到酶活性位点或结合口袋和界面的途径仍然具有挑战性。这一研究途径的动机是理解感兴趣的特定大分子系统，并为他们的研究创造一般方法。一种特别重要的蛋白质是SARS-CoV-2主蛋白酶（Mpro），它是冠状病毒复制所必需的，是变体学中许多研究的主题。它既是一个有吸引力的药物靶点，而且由于对药物化合物开发的强烈兴趣，它是研究蛋白质抑制的最新方法的一个指标。本文提出了一种表征蛋白质变构的计算方法，并将其用于Mpro的研究。我们提出了蛋白质的c端尾部在变构调节中的作用，并警告了一些不直观的陷阱，这些陷阱可能会阻碍蛋白质二面角在传递变构信号中的作用的研究。

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

Proteins-Structure Function and Bioinformatics 生物-生化与分子生物学

CiteScore

5.90

自引率

3.40%

发文量

172

审稿时长

3 months

期刊介绍： PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.