Sequence and structural comparison of thermophilic phosphoglycerate kinases with a mesophilic equivalent

The monomeric glycolytic enzyme phosphoglycerate kinase (PGK) has been used as a model system to study protein thermostability. The primary sequence of this enzyme has been elucidated from 47 species to date. Although only 42 amino acids are totally conserved, most of which line the active site cleft, the protein is structurally conserved. This is achieved by making conservative changes to maintain the same secondary and tertiary folds. The crystal structures of 5 PGK enzymes have been solved by X-ray diffraction methods. This paper seeks to use the available information to understand protein thermostability. Although some general mechanisms to increase stability can be determined, different species have adopted a variety of subtle additive changes to achieve greater protein stability. Comparisons have been directly made between the PGK enzyme from yeast, the moderate thermophilic bacterium Bacillus stearothermophilus, the hyperthermophilic bacteria Thermus thermophilus, Thermotoga maritima, and the hyperthermophilic archaea Sulpholobus solfataricus and Methanothermus fervidus.