title: Structural and functional adaptations to extreme temperatures in psychrophilic, mesophilic, and thermophilic DNA ligases.
abstract: Psychrophiles, host of permanently cold habitats, display metabolic fluxes comparable to those exhibited by mesophilic organisms at moderate temperatures. These organisms have evolved by producing, among other peculiarities, cold-active enzymes that have the properties to cope with the reduction of chemical reaction rates induced by low temperatures. The emerging picture suggests that these enzymes display a high catalytic efficiency at low temperatures through an improved flexibility of the structural components involved in the catalytic cycle, whereas other protein regions, if not implicated in catalysis, may be even more rigid than their mesophilic counterparts. In return, the increased flexibility leads to a decreased stability of psychrophilic enzymes. In order to gain further advances in the analysis of the activity/flexibility/stability concept, psychrophilic, mesophilic, and thermophilic DNA ligases have been compared by three-dimensional-modeling studies, as well as regards their activity, surface hydrophobicity, structural permeability, conformational stabilities, and irreversible thermal unfolding. These data show that the cold-adapted DNA ligase is characterized by an increased activity at low and moderate temperatures, an overall destabilization of the molecular edifice, especially at the active site, and a high conformational flexibility. The opposite trend is observed in the mesophilic and thermophilic counterparts, the latter being characterized by a reduced low temperature activity, high stability and reduced flexibility. These results strongly suggest a complex relationship between activity, flexibility and stability. In addition, they also indicate that in cold-adapted enzymes, the driving force for denaturation is a large entropy change.
authors.affiliation: Laboratory of Biochemistry, Institute of Chemistry B6, University of Liège, B-4000 Liège, Belgium.
authors.forename: Daphné
authors.initials: D
authors.lastname: Georlette
authors.forename: Benjamin
authors.initials: B
authors.lastname: Damien
authors.forename: Vinciane
authors.initials: V
authors.lastname: Blaise
authors.forename: Eric
authors.initials: E
authors.lastname: Depiereux
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: Charles
authors.initials: C
authors.lastname: Gerday
authors.forename: Georges
authors.initials: G
authors.lastname: Feller
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D011088:DNA Ligases / Q000737:chemistry* / Q000502:physiology; D004795:Enzyme Stability; D005453:Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013696:Temperature
chemical_list: D001426:Bacterial Proteins; D011088:DNA Ligases