The short-chain alcohol dehydrogenase from the archaeon Thermococcus sibiricus (TsAdh319) exhibits adaptation to different kinds of stress: high temperature, high salinity, and the presence of organic solvents and denaturants. Previously a comparison of TsAdh319 with close structural homologs revealed an abnormally large number of charged residues on the surface of TsAdh319 tetramer. We further focused on the analysis of hydrogen bonding of TsAdh319 and its structural homologs from thermophilic and mesophilic organisms as a structural factor of adaptation to extreme environment. The calculation and analysis of the dynamics of hydrogen bonds of different kind were performed. In particular, the intramolecular hydrogen bonds of different kind according to their location and the type of a.a. residues involved in the bond were analyzed. TsAdh319 showed the greatest contribution of charged residues to the formation of surface hydrogen bonds, inner hydrogen bonding, and the bonds between different subunits compared to its structural homologs. Molecular dynamics simulations revealed that, of three enzyme molecules analyzed, TsAdh319 shows the least change in the number of hydrogen bonds of different kinds upon a temperature shift from 27 to 85 °C. The greatest changes were observed for a homologous enzyme from a mesophilic host. Only guanidine hydrochloride being a charged agent was able to deactivate TsAdh319. We suggest that the percentage of charged residues plays a key role in the resistance of TsAdh319 to environmental stress. The analysis shows that salt bridges in TsAdh319 serve as a universal instrument of stabilization under different extreme conditions.
Keywords: Hydrogen bonds; Molecular dynamics; Protein adaptation; Short-chain dehydrogenases; Thermostability.
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