Structural basis for the thermal stability of glyceraldehyde-3-phosphate dehydrogenases.

The amino acid sequences of two thermophilic and five mesophilic glyceraldehyde-3-phosphate dehydrogenases have been compared with the known three-dimensional structure of this enzyme to determine the factors responsible for thermal stability. The changes are greatest in the S-loop regions at the center of the tetramer, which show a quantitative increase in hydrophobicity and polarity that can strengthen subunit interactions in a complementary manner. The S-loops also show increases in residue volume and bulk that may indicate a tighter packing at the molecular center. In addition, there are changes in the secondary structural parameters indicating that the helices, in particular, may be more stable in the thermophilic proteins. Increases in the hydrophobicity of domain and subunit contacts for the Thermus aquaticus glyceraldehyde-3-phosphate dehydrogenase may explain why it is the most thermostable protein in this series.