Disulfide isomerization, acceleration

Clearly, the action of prolyl isomerases is not restricted to the slow folding of polypeptide chains with intact disulfides, but they also accelerate the oxidative folding of reduced proteins, which resemble more closely the nascent polypeptide chains as they occur in the endoplasmic reticulum. The simultaneous presence of PPI markedly enhances the efficiency of PDI as a catalyst of disulfide bond formation. Both enzymes act according to their specificity and catalyze the isomerization of prolyl peptide bonds and the formation of disulfide bonds, respectively, in the folding protein chains. It remains to be demonstrated that a similar concerted action of the two enzymes can take place in the course of de novo synthesis and folding of proteins in the cell. 

With the exception of disulfide bonds, all post-translational modifications must be catalyzed by cellular enzymes. The formation of disulfide bonds can occur at appreciable rates in the absence of enzymes and involves two steps (i) the relatively rapid pairing of cysteines to form S-S bonds that do not correspond to those in the native structure and (ii) disulfide rearrangement (20), The isomerization of disulfide bonds to form the correct cysteine pairs that are present in the native protein is slow and represents an important rate limiting step in folding. For this reason the in-vitro refolding of polypeptides containing several cysteines is usually very slow and inefficient. In eucaryotic cells the formation of the correct disulfide bonds is accelerated by the enzyme protein disulfide isomerase or PDI (38,39), PDI is located... 

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