Figure 5.

A simple scenario for protein folding and misfolding hPGK1 enzymes inside the cell. Folding of hPGK1 may occur in vivo spontaneously after its synthesis, as seen by its spontaneous folding in vitro [13] and the fast and spontaneous folding of yeast PGK in living cells ([26,99]). Alternatively, the native state can be reached via interaction of partially folded states with different classes of molecular chaperones. The red arrows indicate steps that may be affected in vivo upon disease-causing mutations, mostly associated with reduced native stability and folding cooperativity [13,46]. The potential targets for pharmacological correction by proteostasis modulators (PM) and pharmacological chaperones (PC) are also indicated.