title: Thermal adaptation of dihydrofolate reductase from the moderate thermophile Geobacillus stearothermophilus.
abstract: The thermal melting temperature of dihydrofolate reductase from Geobacillus stearothermophilus (BsDHFR) is ~30 °C higher than that of its homologue from the psychrophile Moritella profunda. Additional proline residues in the loop regions of BsDHFR have been proposed to enhance the thermostability of BsDHFR, but site-directed mutagenesis studies reveal that these proline residues contribute only minimally. Instead, the high thermal stability of BsDHFR is partly due to removal of water-accessible thermolabile residues such as glutamine and methionine, which are prone to hydrolysis or oxidation at high temperatures. The extra thermostability of BsDHFR can be obtained by ligand binding, or in the presence of salts or cosolvents such as glycerol and sucrose. The sum of all these incremental factors allows BsDHFR to function efficiently in the natural habitat of G. stearothermophilus, which is characterized by temperatures that can reach 75 °C.
authors.affiliation: School of Chemistry, Cardiff University , Main Building, Park Place, Cardiff CF10 3AT, United Kingdom.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Guo
authors.forename: Louis Y P
authors.initials: LY
authors.lastname: Luk
authors.forename: E Joel
authors.initials: EJ
authors.lastname: Loveridge
authors.forename: Rudolf K
authors.initials: RK
authors.lastname: Allemann
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004795:Enzyme Stability; D001411:Geobacillus stearothermophilus / Q000201:enzymology*; D006358:Hot Temperature; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009994:Osmolar Concentration; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012997:Solvents / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D012997:Solvents; D013762:Tetrahydrofolate Dehydrogenase
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