The role of the C-terminal lysine in the hinge bending mechanism of yeast phosphoglycerate kinase

Treatment of yeast phosphoglycerate kinase (PGK) with trypsin results in a fourfold increase in the Vmax of this enzyme, without affecting the Km. This activation is shown to be due to the removal of the C-terminal lysine residue. The C-terminal sequence folds back over the N-terminal domain and contacts the extreme N-terminal sequence which folds onto the C-terminal domain, thus making many of the inter-domain contacts in this two domain protein. Previous studies have shown that this C-terminal region is important in mediating the conformational changes required during catalysis by yeast PGK. Observation of the three-dimensional structure of this enzyme suggests that removal of the C-terminal lysine residue will strengthen the interaction between K5 and E413. This indicates that this salt bridge stabilises the enzyme in the higher activity form, while the presence of K415 reduces the strength of that interaction.