酶的功能是如何进化的:基因、结构和动力学的观点。

IF 4.9 Q1 BIOPHYSICS
Biophysical reviews Pub Date : 2025-04-11 eCollection Date: 2025-04-01 DOI:10.1007/s12551-025-01314-w
Nicolás Fuentes-Ugarte, Martin Pereira-Silva, Isaac Cortes-Rubilar, Gabriel Vallejos-Baccelliere, Victoria Guixé, Victor Castro-Fernandez
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引用次数: 0

摘要

了解酶功能的出现或丧失包括几种方法,如遗传、结构和动力学研究。混杂酶活性被认为是新酶功能出现的起点,例如通过新功能化和亚功能化等遗传模型。在这两种情况下,中性进化将修复基因冗余,这对于放松功能限制和允许特定突变驱动创新至关重要。酶活性的进化具有结构基础,基因突变改变了活性位点结构、构象动力学或相互作用网络,从而导致了上位相互作用至关重要的酶功能的创造、增强或限制。这些结构变化影响了所描述的动力学机制,如基态稳定(亲和),过渡态稳定(催化),或两者的结合。案例研究跨越不同的酶家族说明这些原则,强调遗传,结构和动力学方法之间的相互作用。最后,我们讨论了理解进化机制的重要性及其对生物医学和工业应用的蛋白质工程和药物设计的影响。然而,这些研究强调,进一步的实验进化数据收集是必要的,以便能够训练用于生物技术应用的先进机器学习模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
How enzyme functions evolve: genetic, structural, and kinetic perspectives.

Understanding the emergence or loss of enzyme functions comprises several approaches, such as genetic, structural, and kinetic studies. Promiscuous enzyme activities have been proposed as starting points for the emergence of novel enzyme functions, for example, through genetic models such as neofunctionalization and subfunctionalization. In both cases, neutral evolution would fix gene redundancy, critical in relaxing functional constraints and allowing specific mutations to drive innovation. The evolution of enzyme activities has a structural basis, with genetic mutations modifying the active site architecture, conformational dynamics, or interaction networks, which leads to the creation, enhancement, or restriction of enzyme functions where epistatic interactions are crucial. These structural changes impact the described kinetic mechanisms like ground-state stabilization (affinity), transition-state stabilization (catalysis), or a combination of both. Case studies across diverse enzyme families illustrate these principles, emphasizing the interplay between genetic, structural, and kinetic approaches. Finally, we discuss the importance of understanding evolutionary mechanisms and their impact on protein engineering and drug design for biomedical and industrial applications. However, these studies highlight that further experimental evolutionary data collection is necessary to enable the training of advanced machine learning models for use in biotechnological applications.

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来源期刊
Biophysical reviews
Biophysical reviews Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
8.90
自引率
0.00%
发文量
93
期刊介绍: Biophysical Reviews aims to publish critical and timely reviews from key figures in the field of biophysics. The bulk of the reviews that are currently published are from invited authors, but the journal is also open for non-solicited reviews. Interested authors are encouraged to discuss the possibility of contributing a review with the Editor-in-Chief prior to submission. Through publishing reviews on biophysics, the editors of the journal hope to illustrate the great power and potential of physical techniques in the biological sciences, they aim to stimulate the discussion and promote further research and would like to educate and enthuse basic researcher scientists and students of biophysics. Biophysical Reviews covers the entire field of biophysics, generally defined as the science of describing and defining biological phenomenon using the concepts and the techniques of physics. This includes but is not limited by such areas as: - Bioinformatics - Biophysical methods and instrumentation - Medical biophysics - Biosystems - Cell biophysics and organization - Macromolecules: dynamics, structures and interactions - Single molecule biophysics - Membrane biophysics, channels and transportation
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