当前位置：
X-MOL 学术
›
J. Am. Chem. Soc.
›
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.)
Harnessing Conformational Plasticity to Generate Designer Enzymes
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-06-04 , DOI: 10.1021/jacs.0c04924 Rory M Crean 1 , Jasmine M Gardner 1 , Shina C L Kamerlin 1
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-06-04 , DOI: 10.1021/jacs.0c04924 Rory M Crean 1 , Jasmine M Gardner 1 , Shina C L Kamerlin 1
Affiliation
|
Recent years have witnessed an explosion of interest in understanding the role of conformational dynamics both in the evolution of new enzymatic activities from existing enzymes and in facilitating the emergence of enzymatic activity de novo on scaffolds that were previously non-catalytic. There are also an increasing number of examples in the literature of targeted engineering of conformational dynamics being successfully used to alter enzyme selectivity and activity. Despite the obvious importance of conformational dynamics to both enzyme function and evolvability, many (although not all) computational design approaches still focus either on pure sequence-based approaches or on using structures with limited flexibility to guide the design. However, there exist a wide variety of computational approaches that can be (re)purposed to introduce conformational dynamics as a key consideration in the design process. Coupled with laboratory evolution and more conventional existing sequence- and structure-based approaches, these techniques provide powerful tools for greatly expanding the protein engineering toolkit. This Perspective provides an overview of evolutionary studies that have dissected the role of conformational dynamics in facilitating the emergence of novel enzymes, as well as advances in computational approaches that allow one to target conformational dynamics as part of enzyme design. Harnessing conformational dynamics in engineering studies is a powerful paradigm with which to engineer the next generation of designer biocatalysts.
中文翻译：
利用构象可塑性来生成设计酶
近年来，人们对理解构象动力学的作用产生了浓厚的兴趣，无论是在现有酶进化出新的酶活性方面，还是在促进以前非催化的支架上酶活性从头出现方面。文献中也有越来越多的构象动力学靶向工程成功用于改变酶选择性和活性的例子。尽管构象动力学对酶功能和进化性具有明显的重要性，但许多（尽管不是全部）计算设计方法仍然侧重于纯基于序列的方法或使用灵活性有限的结构来指导设计。然而，存在多种计算方法，可以（重新）用于引入构象动力学作为设计过程中的关键考虑因素。与实验室进化和更传统的现有基于序列和结构的方法相结合，这些技术为极大扩展蛋白质工程工具包提供了强大的工具。本视角概述了进化研究，这些研究剖析了构象动力学在促进新型酶出现中的作用，以及计算方法的进展，使人们能够将构象动力学作为酶设计的一部分。在工程研究中利用构象动力学是设计下一代生物催化剂的强大范例。
更新日期：2020-06-04
中文翻译：
利用构象可塑性来生成设计酶
近年来，人们对理解构象动力学的作用产生了浓厚的兴趣，无论是在现有酶进化出新的酶活性方面，还是在促进以前非催化的支架上酶活性从头出现方面。文献中也有越来越多的构象动力学靶向工程成功用于改变酶选择性和活性的例子。尽管构象动力学对酶功能和进化性具有明显的重要性，但许多（尽管不是全部）计算设计方法仍然侧重于纯基于序列的方法或使用灵活性有限的结构来指导设计。然而，存在多种计算方法，可以（重新）用于引入构象动力学作为设计过程中的关键考虑因素。与实验室进化和更传统的现有基于序列和结构的方法相结合，这些技术为极大扩展蛋白质工程工具包提供了强大的工具。本视角概述了进化研究，这些研究剖析了构象动力学在促进新型酶出现中的作用，以及计算方法的进展，使人们能够将构象动力学作为酶设计的一部分。在工程研究中利用构象动力学是设计下一代生物催化剂的强大范例。
京公网安备 11010802027423号