{"title":"远端位点在酶工程中的作用","authors":"Jie Gu , Yan Xu , Yao Nie","doi":"10.1016/j.biotechadv.2023.108094","DOIUrl":null,"url":null,"abstract":"<div><p>The limitations associated with natural enzyme catalysis have triggered the rise of the field of protein engineering. Traditional rational design was based on the analysis of protein structural information and catalytic mechanisms to identify key active sites or ligand binding sites to reshape the substrate pocket. The role and significance of functional sites in the active center have been studied extensively. With a deeper understanding of the structure–catalysis relationship map, the entire protein molecule can be filled with residues that play a substantial role in its structure and function. However, the catalytic mechanism underlying distal mutations remains unclear. The aim of this review was to highlight the criticality of the distal site in enzyme engineering based on the following three aspects: What can distal mutations exert on function from mutability landscape? How do distal sites influence enzyme function? How to predict and design distal mutations? This review provides insights into the catalytic mechanism of enzymes from the global interaction network, knowledge from sequence-structure-dynamics-function relationships, and strategies for distal mutation-based protein engineering.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":null,"pages":null},"PeriodicalIF":12.1000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"6","resultStr":"{\"title\":\"Role of distal sites in enzyme engineering\",\"authors\":\"Jie Gu , Yan Xu , Yao Nie\",\"doi\":\"10.1016/j.biotechadv.2023.108094\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The limitations associated with natural enzyme catalysis have triggered the rise of the field of protein engineering. Traditional rational design was based on the analysis of protein structural information and catalytic mechanisms to identify key active sites or ligand binding sites to reshape the substrate pocket. The role and significance of functional sites in the active center have been studied extensively. With a deeper understanding of the structure–catalysis relationship map, the entire protein molecule can be filled with residues that play a substantial role in its structure and function. However, the catalytic mechanism underlying distal mutations remains unclear. The aim of this review was to highlight the criticality of the distal site in enzyme engineering based on the following three aspects: What can distal mutations exert on function from mutability landscape? How do distal sites influence enzyme function? How to predict and design distal mutations? This review provides insights into the catalytic mechanism of enzymes from the global interaction network, knowledge from sequence-structure-dynamics-function relationships, and strategies for distal mutation-based protein engineering.</p></div>\",\"PeriodicalId\":8946,\"journal\":{\"name\":\"Biotechnology advances\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.1000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biotechnology advances\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0734975023000010\",\"RegionNum\":1,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology advances","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0734975023000010","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
The limitations associated with natural enzyme catalysis have triggered the rise of the field of protein engineering. Traditional rational design was based on the analysis of protein structural information and catalytic mechanisms to identify key active sites or ligand binding sites to reshape the substrate pocket. The role and significance of functional sites in the active center have been studied extensively. With a deeper understanding of the structure–catalysis relationship map, the entire protein molecule can be filled with residues that play a substantial role in its structure and function. However, the catalytic mechanism underlying distal mutations remains unclear. The aim of this review was to highlight the criticality of the distal site in enzyme engineering based on the following three aspects: What can distal mutations exert on function from mutability landscape? How do distal sites influence enzyme function? How to predict and design distal mutations? This review provides insights into the catalytic mechanism of enzymes from the global interaction network, knowledge from sequence-structure-dynamics-function relationships, and strategies for distal mutation-based protein engineering.
期刊介绍:
Biotechnology Advances is a comprehensive review journal that covers all aspects of the multidisciplinary field of biotechnology. The journal focuses on biotechnology principles and their applications in various industries, agriculture, medicine, environmental concerns, and regulatory issues. It publishes authoritative articles that highlight current developments and future trends in the field of biotechnology. The journal invites submissions of manuscripts that are relevant and appropriate. It targets a wide audience, including scientists, engineers, students, instructors, researchers, practitioners, managers, governments, and other stakeholders in the field. Additionally, special issues are published based on selected presentations from recent relevant conferences in collaboration with the organizations hosting those conferences.