4.7 Article

Non-synonymous substitution of evolutionarily conserved residue in Tau class glutathione transferases alters structural and catalytic features

期刊

出版社

ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.12.040

关键词

Glutathione S-transferase; Glutathione; Biochemical experiment; Crystallography; Molecular dynamics simulations; Agricultural biotechnology

资金

  1. National Natural Science Founda-tion of China [32071486]

向作者/读者索取更多资源

This study reveals the importance of the interaction between the Ile residue and GSH for the structural stability and catalytic function of plant-specific tau glutathione transferases (GSTs). The substitution of Ile by Thr significantly decreases the affinity and catalytic efficiency of the GSTs. Crystallography studies and molecular dynamics simulations show that this conversion leads to hydrogen bond recombination and conformational rearrangement of GST active cavity.
Plant-specific tau glutathione transferases (GSTs) are basically involved in catalysing gamma-glutathione (GSH)dependent conjugation reactions with pesticides and herbicides, which play an important role in the detoxification of pollutants. Given the lack of systematic biochemical and structural information on tau GSTs, the study of their mediated defence mechanisms against toxic compounds has been greatly hindered. Here, we reveal the importance of the Ile residue closely interacting with GSH for the structural stability and catalytic function of GST. Evolutionary conservation analysis indicated that the crucial G-site Ile55 in the SbGSTU6 was converted to Thr53 of SbGSTU7. The comparative biochemical data on SbGSTU6, SbGSTU7 and their mutants showed that the substitution of Ile by Thr caused significant decrease in the affinity and catalytic efficiency of the GSTs. The unfavourable structural flexibility and pKa distribution of the active cavity residues were also demonstrated. Crystallography studies and molecular dynamics simulations showed that the conversion resulted in the hydrogen bond recombination with GSH and conformational rearrangement of GST active cavity, in which the Ile residue was more conducive to the formation of enzyme substrate complexes. The extensive biochemical and structural data not only reveal the critical role of the conserved G-site Ile residue in catalysing GSH-conjugate reactions but also provide valuable resources for the development of GST engineering in analytical and agricultural biotechnology.

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。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据