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

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

doi:10.3389/fchem.2021.661008

Abstract

Active sites of enzymes play a vital role in catalysis, and researchhas been focused on the interactions between active sites and substrates to understand the biocatalytic process. However, the 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 two major research methodswith non-active sites as direct targets, including understanding 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 on non-active sites. Finally, we summarized the results of bioinformatic analysisof mining non-active sites as targets for protein engineering.

Highlights

Enzymes are used widely in industrial production, energy development, medical and health industries, and life science researchas biocatalysts
Amino acid residues around the active sites are structurally and functionally related (Ali et al, 2018; Ali et al, 2019). In this mini-review, we focused on the progress in research on non-active sites and summarized their application fields, locations in the enzyme structure, molecular mechanisms, and bioinformaticmining methods
We listed the locations of effective non-active sites and bioinformatic tools for mining the possible non-active sites

Summary

INTRODUCTION

Enzymes are used widely in industrial production, energy development, medical and health industries, and life science researchas biocatalysts. Each enzyme molecule has active sites related to its function. These active sites are usually located deep in the catalytic cavity. Poudel verified through computational approaches that regions around the active sites of the enzyme play key roles in the discrimination of CO2 and O2 binding to the enzyme (Poudel et al, 2020). In order to understand the relationship between the structure and function of enzymes and to change the catalytic performance of enzymes, active sites are often the preferred mutation sites for protein engineering. In some functionally different enzyme families, studying the active site alone cannot comprehensively explain the catalytic mechanism of the entire enzyme family. O-GlcNAc transferase Meso-diaminopimelate dehydrogenase (StDAPDH) Human DNA polymerase β Exo-inulinase

A Mini-Review on Non-active Sites

Findings

CONCLUSION AND PERSPECTIVES