AUTHOR=Wang Xiaoxiao , Ma Qinyuan , Shen Jian , Wang Bin , Gao Xiuzhen , Zhao Liming 

TITLE=Application Fields, Positions, and Bioinformatic Mining of Non-active Sites: A Mini-Review

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.661008

DOI=10.3389/fchem.2021.661008

ISSN=2296-2646

ABSTRACT=Active sites of enzymes play a vital role in catalysis. Research has been focused on the interactions between active sites and substrates to understand the biocatalytic process. However, some non-active sites distal to the catalytic cavity also participate in catalysis by maintaining the catalytic conformations. Therefore, some researchers have begun to investigate the roles of non-active sites in proteins, especially for enzyme families with different functions. In this mini-review, we focused on recent progress in research on non-active sites of enzymes. First, we outlined the two major research fields with non-active sites as direct targets, including understanding of enzymatic mechanisms and enzyme engineering. Second, we classified the positions of reported non-active sites in enzyme structures and studied the molecular mechanisms underlying their functions, according to the literature related to non-active sites. Finally, we summarized the bioinformatics analysis on mining non-active sites as targets for protein engineering.