Evolution of tunnels in α/β-hydrolase fold proteins—What can we learn from studying epoxide hydrolases?

by Maria Bz ówka, Karolina Mitusińska, Agata Raczyńska, Tomasz Skalski, Aleksandra Samol, Weronika Bagrowska, Tomasz Magdziarz, Artur Góra The evolutionary variability of a protein’s residues is highly dependent on protein region and function. Solvent-exposed residues, excluding those at interaction interfaces, are more variable than buried residues whereas active site residues are considered to be conserved. The abovementioned rul es apply also to α/β-hydrolase fold proteins—one of the oldest and the biggest superfamily of enzymes with buried active sites equipped with tunnels linking the reaction site with the exterior. We selected soluble epoxide hydrolases as representative of this family to conduct the first systemati c study on the evolution of tunnels. We hypothesised that tunnels are lined by mostly conserved residues, and are equipped with a number of specific variable residues that are able to respond to evolutionary pressure. The hypothesis was confirmed, and we suggested a general and detailed way of the t unnels’ evolution analysis based on entropy values calculated for tunnels’ residues. We also found three different cases of entropy distribution among tunnel-lining residues. These observations can be applied for protein reengineering mimicking the natural evolution process. We propose a ‘perf oration’ mechanism for new tunnels designvia the merging of internal cavities or protein surface perforation. Based on the literature data, such a strat...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research