Structural highlights
Publication Abstract from PubMed
Biochemical analysis of enantioselective short-chain alcohol dehydrogenase from the hyperthermophilic archaeon Thermococcus sibiricus (TsAdh319) revealed unique polyextremophilic properties of the enzyme - half-life of 1 h at 100 degrees C, tolerance to high salt (up to 4 M) and organic solvents (50% v/v) concentrations. To elucidate the molecular basis of TsAdh319 polyextremophilicity, we determined the crystal structure of the enzyme in a binary complex with 5-hydroxy-NADP at 1.68 A resolution. TsAdh319 has a tetrameric structure both in the crystals and in solution with an intersubunit disulfide bond. The substrate-binding pocket is hydrophobic, spacious and open that is consistent with the observed promiscuity in substrate specificity of TsAdh319. The present study revealed an extraordinary number of charged residues on the surface of TsAdh319, 70% of which were involved in ion pair interactions. Further we compared the structure of TsAdh319 with the structures of other homologous short-chain dehydrogenases/reductases (SDRs) from thermophilic and mesophilic organisms. We found that TsAdh319 has the highest arginine and aspartate + glutamate contents compared to the counterparts. The frequency of occurrence of salt bridges on the surface of TsAdh319 is the highest among the SDRs under consideration. No differences in the proline, tryptophan, and phenylalanine contents are observed; the compactness of the protein core of TsAdh319, the monomer and tetramer organization do not differ from that of the counterparts. We suggest that the unique thermostability of TsAdh319 is associated with the rigidity and simultaneous "resilience" of the structure provided by a compact hydrophobic core and a large number of surface ion pairs. An extensive salt bridge network also might maintain the structural integrity of TsAdh319 in high salinity.
Structural insight into the molecular basis of polyextremophilicity of short-chain alcohol dehydrogenase from the hyperthermophilic archaeon Thermococcus sibiricus.,Bezsudnova EY, Boyko KM, Polyakov KM, Dorovatovskiy PV, Stekhanova TN, Gumerov VM, Ravin NV, Skryabin KG, Kovalchuk MV, Popov VO Biochimie. 2012 Dec;94(12):2628-38. doi: 10.1016/j.biochi.2012.07.024. Epub 2012 , Aug 5. PMID:22885278[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Bezsudnova EY, Boyko KM, Polyakov KM, Dorovatovskiy PV, Stekhanova TN, Gumerov VM, Ravin NV, Skryabin KG, Kovalchuk MV, Popov VO. Structural insight into the molecular basis of polyextremophilicity of short-chain alcohol dehydrogenase from the hyperthermophilic archaeon Thermococcus sibiricus. Biochimie. 2012 Dec;94(12):2628-38. doi: 10.1016/j.biochi.2012.07.024. Epub 2012 , Aug 5. PMID:22885278 doi:https://dx.doi.org/10.1016/j.biochi.2012.07.024
