The Hairpin Basis for the Structural Thermostability and the Functional Thermoactivity of Aldolase B

Thermostability is important for thermoactivity of proteins including enzymes. However, it is still challenging to pinpoint specific structural factors for different temperature thresholds to initiate their specific structural and functional perturbations. Here, graph theory was used as a novel tool to investigate the role of little hairpins in regulating the structural thermostability and the functional thermo-activity of aldolase B and its prevalent A149P mutant by analyzing their temperature-dependent crystal structures. The results showed that the biggest little hairpin with the minimal topological loop size and strength may determine the temperature thresholds for the changes in their secondary and tertiary structures and specific catalytic activities. Further, a highly conserved thermo-stable little hairpin anchor may facilitate the flexible thermoactivity of this isoenzyme. Thus, this computational study may provide important clues for the structural thermostability and the functional thermoactivity of proteins including enzymes. (140 words) Category computational biochemistry; biophysics; graph theory; network analysis; structural bioinformatics