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工程化蛋白质功能的别构调控。

Engineering an Allosteric Control of Protein Function.

机构信息

Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033-0850, United States.

Departments of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033-0850, United States.

出版信息

J Phys Chem B. 2021 Feb 25;125(7):1806-1814. doi: 10.1021/acs.jpcb.0c11640. Epub 2021 Feb 10.

Abstract

Allosteric regulation in proteins is fundamental to many important biological processes. Allostery has been employed to control protein functions by regulating protein activity. Engineered allosteric regulation allows controlling protein activity in subsecond time scale and has a broad range of applications, from dissecting spatiotemporal dynamics in biochemical cascades to applications in biotechnology and medicine. Here, we review the concept of allostery in proteins and various approaches to identify allosteric sites and pathways. We then provide an overview of strategies and tools used in allosteric protein regulation and their utility in biological applications. We highlight various classes of proteins, where regulation is achieved through allostery. Finally, we analyze the current problems, critical challenges, and future prospective in achieving allosteric regulation in proteins.

摘要

蛋白质的变构调节是许多重要生物学过程的基础。通过调节蛋白质活性,可以利用变构调节来控制蛋白质的功能。设计的变构调节允许在亚秒时间尺度上控制蛋白质的活性,并且具有广泛的应用,从在生物化学级联中剖析时空动态到生物技术和医学中的应用。在这里,我们回顾了蛋白质变构的概念以及识别变构位点和途径的各种方法。然后,我们提供了变构蛋白调节中使用的策略和工具的概述及其在生物应用中的实用性。我们强调了通过变构调节实现的各种蛋白质类别。最后,我们分析了在蛋白质中实现变构调节方面当前存在的问题、关键挑战和未来展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c521/10658643/4914c27c3908/nihms-1945422-f0002.jpg

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