Structure-function relationship between soluble epoxide hydrolases structure and their tunnel network

Karolina Mitusińska; Piotr Wojsa; Maria Bzówka; Agata Raczyńska; Weronika Bagrowska; Aleksandra Samol; Patryk Kapica; Artur Góra

doi:10.1016/j.csbj.2021.10.042

Structure-function relationship between soluble epoxide hydrolases structure and their tunnel network

Comput Struct Biotechnol J. 2021 Dec 13:20:193-205. doi: 10.1016/j.csbj.2021.10.042. eCollection 2022.

Authors

Karolina Mitusińska¹, Piotr Wojsa¹, Maria Bzówka¹, Agata Raczyńska¹, Weronika Bagrowska¹, Aleksandra Samol¹, Patryk Kapica¹, Artur Góra¹

Affiliation

¹ Tunneling Group, Biotechnology Centre, Silesian University of Technology, Gliwice, Poland.

Abstract

Enzymes with buried active sites maintain their catalytic function via a single tunnel or tunnel network. In this study we analyzed the functionality of soluble epoxide hydrolases (sEHs) tunnel network, by comparing the overall enzyme structure with the tunnel's shape and size. sEHs were divided into three groups based on their structure and the tunnel usage. The obtained results were compared with known substrate preferences of the studied enzymes, as well as reported in our other work evolutionary analyses data. The tunnel network architecture corresponded well with the evolutionary lineage of the source organism and large differences between enzymes were observed from long fragments insertions. This strategy can be used during protein re-engineering process for large changes introduction, whereas tunnel modification can be applied for fine-tuning of enzyme.

Keywords: CH65-EH, soluble epoxide hydrolase from an unknown source, sampled in hot springs in China; Protein engineering; Sibe-EH, soluble epoxide hydrolase from an unknown source, sampled in hot springs in Russia; Soluble epoxide hydrolases; StEH1, Solanum tuberosum soluble epoxide hydrolase; Structure–function relationship; TrEH, Trichoderma reesei soluble epoxide hydrolase; Tunnel network; VrEH2, Vigna radiata soluble epoxide hydrolase; bmEH, Bacillus megaterium soluble epoxide hydrolase; hsEH, Homo sapiens soluble epoxide hydrolase; msEH, Mus musculus soluble epoxide hydrolase; sEHs, soluble epoxide hydrolases.