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模块化蛋白质中的变构串扰:功能微调与药物设计。

Allosteric crosstalk in modular proteins: Function fine-tuning and drug design.

作者信息

Abhishek Suman, Deeksha Waghela, Nethravathi Krishnapura Ranganatha, Davari Mehdi D, Rajakumara Eerappa

机构信息

Macromolecular Structural Biology lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Telangana 502284, India.

Department of Studies and Research in organic chemistry (DOS&R in organic chemistry), Tumkur University, Karnataka 572102, India.

出版信息

Comput Struct Biotechnol J. 2023 Oct 10;21:5003-5015. doi: 10.1016/j.csbj.2023.10.013. eCollection 2023.

Abstract

Modular proteins are regulatory proteins that carry out more than one function. These proteins upregulate or downregulate a biochemical cascade to establish homeostasis in cells. To switch the function or alter the efficiency (based on cellular needs), these proteins require different facilitators that bind to a site different from the catalytic (active/orthosteric) site, aka 'allosteric site', and fine-tune their function. These facilitators (or effectors) are allosteric modulators. In this Review, we have discussed the allostery, characterized them based on their mechanisms, and discussed how allostery plays an important role in the activity modulation and function fine-tuning of proteins. Recently there is an emergence in the discovery of allosteric drugs. We have also emphasized the role, significance, and future of allostery in therapeutic applications.

摘要

模块化蛋白质是执行多种功能的调节蛋白。这些蛋白质上调或下调生化级联反应,以在细胞中建立体内平衡。为了切换功能或改变效率(基于细胞需求),这些蛋白质需要不同的促进因子,这些促进因子与不同于催化(活性/正构)位点的位点结合,即“变构位点”,并微调其功能。这些促进因子(或效应物)是变构调节剂。在本综述中,我们讨论了变构现象,根据其机制对其进行了表征,并讨论了变构如何在蛋白质的活性调节和功能微调中发挥重要作用。最近,变构药物的发现不断涌现。我们还强调了变构在治疗应用中的作用、意义和未来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc79/10589753/60dca21dadd8/ga1.jpg

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