Protein disulfide isomerase
|protein disulfide isomerase family A, member 2|
|Locus||Chr. 16 p13.3|
|protein disulfide isomerase family A, member 3|
|Locus||Chr. 15 q15|
|protein disulfide isomerase family A, member 4|
|Locus||Chr. 7 q35|
|protein disulfide isomerase family A, member 5|
|Locus||Chr. 3 q21.1|
|protein disulfide isomerase family A, member 6|
|Locus||Chr. 2 p25.1|
Protein disulfide isomerase or PDI (EC 188.8.131.52) is an enzyme in the endoplasmic reticulum in eukaryotes or periplasmic space of prokaryotes that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold. This allows proteins to quickly find the correct arrangement of disulfide bonds in their fully-folded state, and therefore the enzyme acts to catalyze protein folding. In contrast, reduced (dithiol) form of PDI is able to catalyse a reduction of mispaired thiol residues of a particular substrate, acting as an isomerase. Therefore, PDI is capable of catalyzing the post-translational disulfide exchange. Such exchange reactions can occur intramolecularly, leading to the rearrangement of disulphide bonds in a single protein.
Another major function of PDI relates to its activity as a chaperone, i.e., it aids wrongly-folded proteins to reach a correctly-folded state without the aid of enzymatic disulfide shuffling.
PDI has been found to be involved in the breaking of bonds on the HIV gp120 protein during HIV infection of CD4 positive cells, and is required for HIV infection of lymphocytes and monoctyes. Some studies have shown it to be available for HIV infection on the surface of the cell clustered around the CD4 protein. Yet conflicting studies have shown that it is not available on the cell surface, but instead is found in significant amounts in the blood plasma.
Oxidized PDI can catalyze the formation of a disulfide bridge. This reduces PDI and a protein called Ero1 oxidizes it again.
Assays used for PDI activity
Insulin Turbidity Assay: PDI breaks the two disulfide bonds between two insulin (a and b) chains that results in precipitation of b chain. This precipitation can be monitored at 620 nm, which is indirectly used monitor PDI activity. Sensitivity of this assay is in micromolar range.
Di-E-GSSG assay: This is the fluorometric assay that can detect picomolar quantities of PDI and therefore is the most sensitive assay to date for detecting PDI activity. Di-E-GSSG has two eosin molecules attached to oxidized glutathione (GSSG). The proximity of eosin molecules leads to the quenching of its fluorescence. However, upon breakage of disulfide bond by PDI, fluorescence increases 70-fold.
- Lundström J, Holmgren A (1990). "Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity". J. Biol. Chem. 265 (16): 9114–20. PMID 2188973.
- Lyles MM, Gilbert HF (1991). "Catalysis of the oxidative folding of ribonuclease A by protein disulfide isomerase: dependence of the rate on the composition of the redox buffer". Biochemistry. 30 (3): 613–9. PMID 1988050.
- Raturi A, Mutus B (2007). "Characterization of redox state and reductase activity of protein disulfide isomerase under different redox environments using a sensitive fluorescent assay". Free Radic. Biol. Med. 43 (1): 62–70. doi:10.1016/j.freeradbiomed.2007.03.025. PMID 17561094.
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