期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 428, 期 2, 页码 253-267出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2015.11.010
关键词
protein domain evolution; enzyme function evolution; catalytic residues; protein domain superfamilies; enzyme reaction chemistry
资金
- Medical Research Council
- Wellcome Trust
- European Molecular Biology Laboratory
- BBSRC [BB/K020013/1] Funding Source: UKRI
- MRC [MR/K020420/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K020013/1] Funding Source: researchfish
- Medical Research Council [MR/K020420/1] Funding Source: researchfish
Enzymes, as biological catalysts, form the basis of all forms of life. How these proteins have evolved their functions remains a fundamental question in biology. Over 100 years of detailed biochemistry studies, combined with the large volumes of sequence and protein structural data now available, means that we are able to perform large-scale analyses to address this question. Using a range of computational tools and resources, we have compiled information on all experimentally annotated changes in enzyme function within 379 structurally defined protein domain superfamilies, linking the changes observed in functions during evolution to changes in reaction chemistry. Many superfamilies show changes in function at some level, although one function often dominates one superfamily. We use quantitative measures of changes in reaction chemistry to reveal the various types of chemical changes occurring during evolution and to exemplify these by detailed examples. Additionally, we use structural information of the enzymes active site to examine how different superfamilies have changed their catalytic machinery during evolution. Some superfamilies have changed the reactions they perform without changing catalytic machinery. In others, large changes of enzyme function, in terms of both overall chemistry and substrate specificity, have been brought about by significant changes in catalytic machinery. Interestingly, in some superfamilies, relatives perform similar functions but with different catalytic machineries. This analysis highlights characteristics of functional evolution across a wide range of superfamilies, providing insights that will be useful in predicting the function of uncharacterised sequences and the design of new synthetic enzymes. (C) 2015 The Authors. Published by Elsevier Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据