Engineering enzyme access tunnels

This publication doesn't include Faculty of Arts. It includes Faculty of Science. Official publication website can be found on muni.cz.

Authors

KOKKONEN Piia Pauliina BEDNÁŘ David PINTO G. PROKOP Zbyněk DAMBORSKÝ Jiří

Type Article in Periodical
Magazine / Source BIOTECHNOLOGY ADVANCES
MU Faculty or unit

Faculty of Science

Citation
Web http://dx.doi.org/10.1016/j.biotechadv.2019.04.008
Doi http://dx.doi.org/10.1016/j.biotechadv.2019.04.008
Keywords Tunnel; Channel; Ligand binding; Pathway; Pore; Product release; Protein design; Protein engineering; Substrate entry; Dynamics
Description Enzymes are efficient and specific catalysts for many essential reactions in biotechnological and pharmaceutical industries. Many times, the natural enzymes do not display the catalytic efficiency, stability or specificity required for these industrial processes. The current enzyme engineering methods offer solutions to this problem, but they mainly target the buried active site where the chemical reaction takes place. Despite being many times ignored, the tunnels and channels connecting the environment with the active site are equally important for the catalytic properties of enzymes. Changes in the enzymatic tunnels and channels affect enzyme activity, specificity, promiscuity, enantioselectivity and stability. This review provides an overview of the emerging field of enzyme access tunnel engineering with case studies describing design of all the aforementioned properties. The software tools for the analysis of geometry and function of the enzymatic tunnels and channels and for the rational design of tunnel modifications will also be discussed. The combination of new software tools and enzyme engineering strategies will provide enzymes with access tunnels and channels specifically tailored for individual industrial processes.
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