Structural insight into the molecular basis of polyextremophilicity of short-chain alcohol dehydrogenase from the hyperthermophilic archaeon Thermococcus sibiricus

► We report the first X-ray structure of archaeal short-chain alcohol dehydrogenase. ► The enzyme revealed a half-life of 1 h at 100 °C, tolerance to organic solvents. ► The TsAdh319 protein core compactness does not differ from that of the counterparts. ► We found an extraordinary number of charged residues on the surface of TsAdh319. ► Nearly 70% of charged groups are involved in ion pair interactions.