Protein disulfide-isomerase active site

Vuori, K., Pihlajaniemi, T., Myllyla, R. and Kivirikko, K.I. (1992) Site-directed mutagenesis of human protein disulfide isomerase - effect on the assembly, activity and endoplasmic-reticulum retention of human prolyl 4-hydroxylase in Spodoptera frugiperda insect cells. EMBO JoumalW, 4213-4217. 

If there are three or more -SH groups in a chain some incorrect pairing may, and often does, occur. Tire protein disulfide isomerases break these bonds and allow new ones to form.92 The active sites of these isomerases contain pairs of -SH groups which can be oxidized to internal -S-S- bridges by NAD+-dependent enzymes. These enzymes and their relatives thioredoxin and glutaredoxin are discussed further in Box 15-C. Glutathione and oxidation-reduction buffering are considered in Box 11-B. 

Mazzarella, R. A., Srinivasan, M., Haugejorden, S. M., and Green, M. (1990). ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase. J. Biol. Chem. 265,1094-1101. 

The efficient formation of disulfide bonds In the lumen of the ER depends on the enzyme protein disulfide isomerase (PDI), which Is present In all eukaryotic cells. This enzyme Is especially abundant In the ER of secretory cells In such organs as the liver and pancreas, where large quantities of proteins that contain disulfide bonds are produced. As shown in Figure 16-19a, the disulfide bond in the active site of PDI can be readily transferred to a protein by two sequential thiol-disulfide transfer reactions. The reduced PDI generated by this reaction is returned to an oxidized form by the action of an ER-resident protein, called Erol, which carries a disulfide bond that can be transferred to PDI. It is not yet understood how Erol itself becomes oxidized. Figure 16-20 depicts the organization of the pathway for protein disulfide-bond formation In the ER lumen and the analogous pathway In bacteria. 

A FIGURE 16-19 Formation and rearrangement of disulfide bonds by protein disulfide isomerase (PDI). PDI contains an active site with two ciosely spaced cysteine residues that are easily interconverted between the reduced dithiol form and the oxidized disulfide form. Numbered red arrows indicate the sequence of electron transfers. Yellow bars represent disulfide bonds, (a) In the formation of disulfide bonds, the ionized (-S ) form of a cysteine thiol in the substrate protein reacts with the disulfide (S—S) bond in oxidized PDI to form a disulfide-bonded... 

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