Isomerization disulfide bonds, formation

Thiol-disulfide isomerization. Disulfide bond formation between Cys residues takes place commonly in the ER during protein biosynthesis. The thiol-disulfide isomerization can occur by either chemical exchange reaction or enzymatic reaction catalyzed by protein disulfide isomerase via mixed disulfide intermediate (protein-S-SG). 

Disulfide bond formation within the individual propeptides precedes folding and trimers are then formed by association of the C-terminal propeptides." Disulfide bonds between the chains are then formed and this formation is most likely catalyzed by PDI." As triple helix formation proceeds, the rate-limiting step in this process is the cis—trans isomerization of peptidyl-Pro bonds. This process can be catalyzed by peptidyl-prolyl cis—trans isomerases (cyclophilins and FKBPs). This activity is required to convert the proline residues to the trans form required for triple helix formation." " " ... 

Disulfide bond formation and the cis-trans isomerization of Pro peptide bonds are catalyzed by specific enzymes. 

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. 

PDI disulfide bond formation and isomerization, folding dehydro ascorb ate reduction dehydro ascorb ate, GSH 10,11,22,23, 44,46,54... 

CATALYSIS OF DISULFIDE BOND FORMATION AND ISOMERIZATION IN Escherichia coli... 

VIII. Disulfide Bond Formation Does Not Interfere with Disulfide Isomerization 298... 

A correct folding of recombinant proteins is regulated by the redox potential of the outer compartments and performed by foldases. These catalyse disulfide bond formation and peptidyl-proline isomerization, prevent protein a regation in inclusion bodies and hamper the proteolysis by cytoplasmic enzymes. The coexptession of eukaryotic foldases leads to an increased yield of eukaryotic recombinant proteins in E. colif Moreover, the supply of reduced glutathione generates favourable environmental conditions for carrying out a correct folding in the periplasm. ... 

Chemical Degradation Deamidation, oxidation, isomerization, proteolysis, aberrant disulfide bond formation, and beta elimination... 

Enzymes assist formation of proper disulfide bonds during folding Isomerization of proline residues can be a rate-limiting step in protein folding Proteins can fold or unfold inside chaperonins GroEL is a cylindrical structure with a... 

At least two major slow processes occur in the folding of disulfide-containing proteins the cis-trans isomerizations of Xaa-Pro peptide bonds and the formation of the correct disulfide bonds. The latter is catalyzed by protein disulfide-isomerase (PDl). This enzyme occurs at high concentration in the endoplasmic reticulum (Hawkins et al., 1991) and there is good experimental evidence that PDl is required for the de novo folding of nascent secretory proteins (Bulleid and Freedman, 1988). Cyclophilins have recently also been localized in the ER (Hasel et al., 1991) and in other compartments of the secretory pathway (Caroni et al., 1991). Their biological function is not known. 

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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