Driving Protein Conformational Cycles in Physiology and Disease: "Frustrated" Amino Acid Interaction Networks Define Dynamic Energy Landscapes: Amino Acid Interaction Networks Change Progressively Along Alpha Tryptophan Synthase's Catalytic Cycle.,BioEssays

当前位置： X-MOL 学术 › BioEssays › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Driving Protein Conformational Cycles in Physiology and Disease: "Frustrated" Amino Acid Interaction Networks Define Dynamic Energy Landscapes: Amino Acid Interaction Networks Change Progressively Along Alpha Tryptophan Synthase's Catalytic Cycle.
BioEssays ( IF 3.2 ) Pub Date : 2020-07-27 , DOI: 10.1002/bies.202000092
Rebecca N D'Amico ₁ , Alec M Murray ₁ , David D Boehr ₁

Affiliation

A general framework by which dynamic interactions within a protein will promote the necessary series of structural changes, or “conformational cycle,” required for function is proposed. It is suggested that the free‐energy landscape of a protein is biased toward this conformational cycle. Fluctuations into higher energy, although thermally accessible, conformations drive the conformational cycle forward. The amino acid interaction network is defined as those intraprotein interactions that contribute most to the free‐energy landscape. Some network connections are consistent in every structural state, while others periodically change their interaction strength according to the conformational cycle. It is reviewed here that structural transitions change these periodic network connections, which then predisposes the protein toward the next set of network changes, and hence the next structural change. These concepts are illustrated by recent work on tryptophan synthase. Disruption of these dynamic connections may lead to aberrant protein function and disease states.

中文翻译：

推动生理学和疾病中的蛋白质构象循环：“受挫的”氨基酸相互作用网络定义动态能量景观：氨基酸相互作用网络沿着 Alpha 色氨酸合酶的催化循环逐渐变化。

提出了一个通用框架，通过该框架，蛋白质内的动态相互作用将促进功能所需的一系列必要的结构变化或“构象循环”。这表明蛋白质的自由能景观偏向于这种构象循环。波动到更高的能量，虽然热可及，构象推动构象循环向前发展。氨基酸相互作用网络被定义为对自由能景观贡献最大的蛋白质内相互作用。一些网络连接在每个结构状态下都是一致的，而另一些网络连接根据构象周期周期性地改变它们的相互作用强度。这里回顾了结构转变改变了这些周期性的网络连接，然后使蛋白质倾向于下一组网络变化，从而导致下一次结构变化。最近关于色氨酸合酶的工作说明了这些概念。这些动态连接的中断可能导致异常的蛋白质功能和疾病状态。

更新日期：2020-08-26

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11