Protein disulfide isomerase (EC 5.3.4.1), or PDI, is an enzyme in the endoplasmic reticulum (ER) in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold.[1][2][3] 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.
Protein disulfide-isomerase
Structural picture of human protein disulfide isomerase (PDB 1BJX)
Protein disulfide-isomerase has two catalytic thioredoxin-like domains (active sites), each containing the canonical CGHC motif, and two non catalytic domains.[4][5][6] This structure is similar to the structure of enzymes responsible for oxidative folding in the intermembrane space of the mitochondria; an example of this is mitochondrial IMS import and assembly (Mia40), which has 2 catalytic domains that contain a CX9C, which is similar to the CGHC domain of PDI.[7] Bacterial DsbA, responsible for oxidative folding, also has a thioredoxin CXXC domain.[8]
Primary structure of protein disulfide isomerase with sequence of domains
Function
Protein folding
PDI displays oxidoreductase and isomerase properties, both of which depend on the type of substrate that binds to protein disulfide-isomerase and changes in protein disulfide-isomerase's redox state.[4] These types of activities allow for oxidative folding of proteins. Oxidative folding involves the oxidation of reduced cysteine residues of nascent proteins; upon oxidation of these cysteine residues, disulfide bridges are formed, which stabilizes proteins and allows for native structures (namely tertiary and quaternary structures).[4]
Regular oxidative folding mechanism and pathway
PDI is specifically responsible for folding proteins in the ER.[6] In an unfolded protein, a cysteine residue forms a mixed disulfide with a cysteine residue in an active site (CGHC motif) of protein disulfide-isomerase. A second cysteine residue then forms a stable disulfide bridge within the substrate, leaving protein disulfide-isomerase's two active-site cysteine residues in a reduced state.[4]
Afterwards, PDI can be regenerated to its oxidized form in the endoplasmic reticulum by transferring electrons to reoxidizing proteins such ER oxidoreductin 1 (Ero 1), VKOR (vitamin K epoxide reductase), glutathione peroxidase (Gpx7/8), and PrxIV (peroxiredoxin IV).[4][9][10][6] Ero1 is thought to be the main reoxidizing protein of PDI, and the pathway of reoxidation of PDI for Ero1 is more understood than that of other proteins.[10] Ero1 accepts electrons from PDI and donates these electrons to oxygen molecules in the ER, which leads to the formation of hydrogen peroxide.[10]
Misfolded protein mechanism
The reduced (dithiol) form of protein disulfide-isomerase is able to catalyze a reduction of a misformed disulfide bridge of a substrate through either reductase activity or isomerase activity.[11] For the reductase method, a misfolded substrate disulfide bond is converted to a pair of reduced cysteine residues by the transfer of electrons from glutathione and NADPH. Afterwards, normal folding occurs with oxidative disulfide bond formation between the correct pairs of substrate cysteine residues, leading to a properly folded protein. For the isomerase method, intramolecular rearrangement of substrate functional groups is catalyzed near the N terminus of each active site.[4] Therefore, protein disulfide-isomerase is capable of catalyzing the post-translational modificationdisulfide exchange.
Redox signaling
In the chloroplasts of the unicellular algaeChlamydomonas reinhardtii the protein disulfide-isomerase RB60 serves as a redox sensor component of an mRNA-binding protein complex implicated in the photoregulation of the translation of psbA, the RNA encoding for the photosystem II core protein D1. Protein disulfide-isomerase has also been suggested to play a role in the formation of regulatory disulfide bonds in chloroplasts.[12]
Other functions
Immune system
Protein disulfide-isomerase helps load antigenic peptides into MHC class I molecules. These molecules (MHC I) are related to the peptide presentation by antigen-presenting cells in the immune response.
Protein disulfide-isomerase has been found to be involved in the breaking of bonds on the HIVgp120 protein during HIV infection of CD4 positive cells, and is required for HIV infection of lymphocytes and monocytes.[13] 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.
Chaperone activity
Another major function of protein disulfide-isomerase relates to its activity as a chaperone; its b' domain aids in the binding of misfolded protein for subsequent degradation.[4] This is regulated by three ER membrane proteins, Protein Kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring kinase 1 (IRE1), and activating transcription factor 6 (ATF6).[4][14] They respond to high levels of misfolded proteins in the ER through intracellular signaling cascades that can activate PDI's chaperone activity.[4] These signals can also inactivate translation of these misfolded proteins, because the cascade travels from the ER to the nucleus.[4]
Activity assays
Insulin turbidity assay: protein disulfide-isomerase 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 650 nm, which is indirectly used to monitor protein disulfide-isomerase activity.[15] Sensitivity of this assay is in micromolar range.
ScRNase assay: protein disulfide-isomerase converts scrambled (inactive) RNase into native (active) RNase that further acts on its substrate.[16] The sensitivity is in micromolar range.
Di-E-GSSG assay: This is the fluorometric assay that can detect picomolar quantities of protein disulfide-isomerase and therefore is the most sensitive assay to date for detecting protein disulfide-isomerase activity.[17] 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 protein disulfide-isomerase, fluorescence increases 70-fold.
Stress and inhibition
Effects of nitrosative stress
Redox dysregulation leads to increases in nitrosative stress in the endoplasmic reticulum. Such adverse changes in the normal cellular environment of susceptible cells, such as neurons, leads to nonfunctioning thiol-containing enzymes.[14] More specifically, protein disulfide-isomerase can no longer fix misfolded proteins once its thiol group in its active site has a nitric monoxide group attached to it; as a result, accumulation of misfolded proteins occurs in neurons, which has been associated with the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[4][14]
Inhibition
Due to the role of protein disulfide-isomerase in a number of disease states, small molecule inhibitors of protein disulfide-isomerase have been developed. These molecules can either target the active site of protein disulfide-isomerase irreversibly[18] or reversibly.[19]
It has been shown that protein disulfide-isomerase activity is inhibited by red wine and grape juice, which could be the explanation for the French paradox.[20]
^Gruber CW, Cemazar M, Heras B, Martin JL, Craik DJ (August 2006). "Protein disulfide isomerase: the structure of oxidative folding". Trends in Biochemical Sciences. 31 (8): 455–64. doi:10.1016/j.tibs.2006.06.001. PMID 16815710.
^ abGalligan JJ, Petersen DR (July 2012). "The human protein disulfide isomerase gene family". Human Genomics. 6 (1): 6. doi:10.1186/1479-7364-6-6. PMC3500226. PMID 23245351.
^ abcdefghijkPerri ER, Thomas CJ, Parakh S, Spencer DM, Atkin JD (2016). "The Unfolded Protein Response and the Role of Protein Disulfide Isomerase in Neurodegeneration". Frontiers in Cell and Developmental Biology. 3: 80. doi:10.3389/fcell.2015.00080. PMC4705227. PMID 26779479.
^Bechtel TJ, Weerapana E (March 2017). "From structure to redox: The diverse functional roles of disulfides and implications in disease". Proteomics. 17 (6): 10.1002/pmic.201600391. doi:10.1002/pmic.201600391. PMC5367942. PMID 28044432.
^ abcSoares Moretti AI, Martins Laurindo FR (March 2017). "Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum". Archives of Biochemistry and Biophysics. The Chemistry of Redox Signaling. 617: 106–119. doi:10.1016/j.abb.2016.11.007. PMID 27889386.
^Erdogan AJ, Riemer J (January 2017). "Mitochondrial disulfide relay and its substrates: mechanisms in health and disease". Cell and Tissue Research. 367 (1): 59–72. doi:10.1007/s00441-016-2481-z. PMID 27543052. S2CID 35346837.
^Hu SH, Peek JA, Rattigan E, Taylor RK, Martin JL (April 1997). "Structure of TcpG, the DsbA protein folding catalyst from Vibrio cholerae". Journal of Molecular Biology. 268 (1): 137–46. doi:10.1006/jmbi.1997.0940. PMID 9149147.
^Manganas P, MacPherson L, Tokatlidis K (January 2017). "Oxidative protein biogenesis and redox regulation in the mitochondrial intermembrane space". Cell and Tissue Research. 367 (1): 43–57. doi:10.1007/s00441-016-2488-5. PMC5203823. PMID 27632163.
^ abcOka OB, Yeoh HY, Bulleid NJ (July 2015). "Thiol-disulfide exchange between the PDI family of oxidoreductases negates the requirement for an oxidase or reductase for each enzyme". The Biochemical Journal. 469 (2): 279–88. doi:10.1042/bj20141423. PMC4613490. PMID 25989104.
^Hatahet F, Ruddock LW (October 2007). "Substrate recognition by the protein disulfide isomerases". The FEBS Journal. 274 (20): 5223–34. doi:10.1111/j.1742-4658.2007.06058.x. PMID 17892489. S2CID 9455925.
^Wittenberg G, Danon A (2008). "Disulfide bond formation in chloroplasts". Plant Science. 175 (4): 459–466. doi:10.1016/j.plantsci.2008.05.011.
^Ryser HJ, Flückiger R (August 2005). "Progress in targeting HIV-1 entry". Drug Discovery Today. 10 (16): 1085–94. doi:10.1016/S1359-6446(05)03550-6. PMID 16182193.
^ abcMcBean GJ, López MG, Wallner FK (June 2017). "Redox-based therapeutics in neurodegenerative disease". British Journal of Pharmacology. 174 (12): 1750–1770. doi:10.1111/bph.13551. PMC5446580. PMID 27477685.
^Lundström J, Holmgren A (June 1990). "Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity". The Journal of Biological Chemistry. 265 (16): 9114–20. doi:10.1016/S0021-9258(19)38819-2. PMID 2188973.
^Lyles MM, Gilbert HF (January 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. doi:10.1021/bi00217a004. PMID 1988050.
^Raturi A, Mutus B (July 2007). "Characterization of redox state and reductase activity of protein disulfide isomerase under different redox environments using a sensitive fluorescent assay". Free Radical Biology & Medicine. 43 (1): 62–70. doi:10.1016/j.freeradbiomed.2007.03.025. PMID 17561094.
^Hoffstrom BG, Kaplan A, Letso R, Schmid RS, Turmel GJ, Lo DC, Stockwell BR (December 2010). "Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins". Nature Chemical Biology. 6 (12): 900–6. doi:10.1038/nchembio.467. PMC3018711. PMID 21079601.
^Kaplan A, Gaschler MM, Dunn DE, Colligan R, Brown LM, Palmer AG, Lo DC, Stockwell BR (April 2015). "Small molecule-induced oxidation of protein disulfide isomerase is neuroprotective". Proceedings of the National Academy of Sciences of the United States of America. 112 (17): E2245-52. Bibcode:2015PNAS..112E2245K. doi:10.1073/pnas.1500439112. PMC4418888. PMID 25848045.
^Galinski CN, Zwicker JI, Kennedy DR (January 2016). "Revisiting the mechanistic basis of the French Paradox: Red wine inhibits the activity of protein disulfide isomerase in vitro". Thrombosis Research. 137: 169–173. doi:10.1016/j.thromres.2015.11.003. PMC4706467. PMID 26585763.
^Ellgaard L, Ruddock LW (January 2005). "The human protein disulphide isomerase family: substrate interactions and functional properties". EMBO Reports. 6 (1): 28–32. doi:10.1038/sj.embor.7400311. PMC1299221. PMID 15643448.
^Appenzeller-Herzog C, Ellgaard L (April 2008). "The human PDI family: versatility packed into a single fold". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783 (4): 535–48. doi:10.1016/j.bbamcr.2007.11.010. PMID 18093543.
External links
Protein Disulfide-Isomerase at the US National Library of Medicine Medical Subject Headings (MeSH)
protein, disulfide, isomerase, protein, disulfide, isomerase, enzyme, endoplasmic, reticulum, eukaryotes, periplasm, bacteria, that, catalyzes, formation, breakage, disulfide, bonds, between, cysteine, residues, within, proteins, they, fold, this, allows, prot. Protein disulfide isomerase EC 5 3 4 1 or PDI is an enzyme in the endoplasmic reticulum ER in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold 1 2 3 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 Protein disulfide isomeraseStructural picture of human protein disulfide isomerase PDB 1BJX IdentifiersSymbol InterProIPR005792Protein disulfide isomeraseIdentifiersEC no 5 3 4 1CAS no 37318 49 3DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteinsprotein disulfide isomerase family A member 2IdentifiersSymbolPDIA2Alt symbolsPDIPNCBI gene64714HGNC14180OMIM608012RefSeqNM 006849UniProtQ13087Other dataLocusChr 16 p13 3Search forStructuresSwiss modelDomainsInterProprotein disulfide isomerase family A member 3IdentifiersSymbolPDIA3Alt symbolsGRP58NCBI gene2923HGNC4606OMIM602046RefSeqNM 005313UniProtP30101Other dataLocusChr 15 q15Search forStructuresSwiss modelDomainsInterProprotein disulfide isomerase family A member 4IdentifiersSymbolPDIA4NCBI gene9601HGNC30167RefSeqNM 004911UniProtP13667Other dataLocusChr 7 q35Search forStructuresSwiss modelDomainsInterProprotein disulfide isomerase family A member 5IdentifiersSymbolPDIA5NCBI gene10954HGNC24811RefSeqNM 006810UniProtQ14554Other dataEC number5 3 4 1LocusChr 3 q21 1Search forStructuresSwiss modelDomainsInterProprotein disulfide isomerase family A member 6IdentifiersSymbolPDIA6Alt symbolsTXNDC7NCBI gene10130HGNC30168RefSeqNM 005742UniProtQ15084Other dataLocusChr 2 p25 1Search forStructuresSwiss modelDomainsInterPro Contents 1 Structure 2 Function 2 1 Protein folding 2 1 1 Regular oxidative folding mechanism and pathway 2 1 2 Misfolded protein mechanism 2 2 Redox signaling 2 3 Other functions 2 3 1 Immune system 2 3 2 Chaperone activity 3 Activity assays 4 Stress and inhibition 4 1 Effects of nitrosative stress 4 2 Inhibition 5 Members 6 References 7 External linksStructure EditProtein disulfide isomerase has two catalytic thioredoxin like domains active sites each containing the canonical CGHC motif and two non catalytic domains 4 5 6 This structure is similar to the structure of enzymes responsible for oxidative folding in the intermembrane space of the mitochondria an example of this is mitochondrial IMS import and assembly Mia40 which has 2 catalytic domains that contain a CX9C which is similar to the CGHC domain of PDI 7 Bacterial DsbA responsible for oxidative folding also has a thioredoxin CXXC domain 8 Primary structure of protein disulfide isomerase with sequence of domainsFunction EditProtein folding Edit PDI displays oxidoreductase and isomerase properties both of which depend on the type of substrate that binds to protein disulfide isomerase and changes in protein disulfide isomerase s redox state 4 These types of activities allow for oxidative folding of proteins Oxidative folding involves the oxidation of reduced cysteine residues of nascent proteins upon oxidation of these cysteine residues disulfide bridges are formed which stabilizes proteins and allows for native structures namely tertiary and quaternary structures 4 Regular oxidative folding mechanism and pathway Edit PDI is specifically responsible for folding proteins in the ER 6 In an unfolded protein a cysteine residue forms a mixed disulfide with a cysteine residue in an active site CGHC motif of protein disulfide isomerase A second cysteine residue then forms a stable disulfide bridge within the substrate leaving protein disulfide isomerase s two active site cysteine residues in a reduced state 4 Afterwards PDI can be regenerated to its oxidized form in the endoplasmic reticulum by transferring electrons to reoxidizing proteins such ER oxidoreductin 1 Ero 1 VKOR vitamin K epoxide reductase glutathione peroxidase Gpx7 8 and PrxIV peroxiredoxin IV 4 9 10 6 Ero1 is thought to be the main reoxidizing protein of PDI and the pathway of reoxidation of PDI for Ero1 is more understood than that of other proteins 10 Ero1 accepts electrons from PDI and donates these electrons to oxygen molecules in the ER which leads to the formation of hydrogen peroxide 10 Misfolded protein mechanism Edit The reduced dithiol form of protein disulfide isomerase is able to catalyze a reduction of a misformed disulfide bridge of a substrate through either reductase activity or isomerase activity 11 For the reductase method a misfolded substrate disulfide bond is converted to a pair of reduced cysteine residues by the transfer of electrons from glutathione and NADPH Afterwards normal folding occurs with oxidative disulfide bond formation between the correct pairs of substrate cysteine residues leading to a properly folded protein For the isomerase method intramolecular rearrangement of substrate functional groups is catalyzed near the N terminus of each active site 4 Therefore protein disulfide isomerase is capable of catalyzing the post translational modification disulfide exchange Redox signaling Edit In the chloroplasts of the unicellular algae Chlamydomonas reinhardtii the protein disulfide isomerase RB60 serves as a redox sensor component of an mRNA binding protein complex implicated in the photoregulation of the translation of psbA the RNA encoding for the photosystem II core protein D1 Protein disulfide isomerase has also been suggested to play a role in the formation of regulatory disulfide bonds in chloroplasts 12 Other functions Edit Immune system Edit Protein disulfide isomerase helps load antigenic peptides into MHC class I molecules These molecules MHC I are related to the peptide presentation by antigen presenting cells in the immune response Protein disulfide isomerase 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 monocytes 13 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 Chaperone activity Edit Another major function of protein disulfide isomerase relates to its activity as a chaperone its b domain aids in the binding of misfolded protein for subsequent degradation 4 This is regulated by three ER membrane proteins Protein Kinase RNA like endoplasmic reticulum kinase PERK inositol requiring kinase 1 IRE1 and activating transcription factor 6 ATF6 4 14 They respond to high levels of misfolded proteins in the ER through intracellular signaling cascades that can activate PDI s chaperone activity 4 These signals can also inactivate translation of these misfolded proteins because the cascade travels from the ER to the nucleus 4 Activity assays EditInsulin turbidity assay protein disulfide isomerase 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 650 nm which is indirectly used to monitor protein disulfide isomerase activity 15 Sensitivity of this assay is in micromolar range ScRNase assay protein disulfide isomerase converts scrambled inactive RNase into native active RNase that further acts on its substrate 16 The sensitivity is in micromolar range Di E GSSG assay This is the fluorometric assay that can detect picomolar quantities of protein disulfide isomerase and therefore is the most sensitive assay to date for detecting protein disulfide isomerase activity 17 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 protein disulfide isomerase fluorescence increases 70 fold Stress and inhibition EditEffects of nitrosative stress Edit Redox dysregulation leads to increases in nitrosative stress in the endoplasmic reticulum Such adverse changes in the normal cellular environment of susceptible cells such as neurons leads to nonfunctioning thiol containing enzymes 14 More specifically protein disulfide isomerase can no longer fix misfolded proteins once its thiol group in its active site has a nitric monoxide group attached to it as a result accumulation of misfolded proteins occurs in neurons which has been associated with the development of neurodegenerative diseases such as Alzheimer s disease and Parkinson s disease 4 14 Inhibition Edit Due to the role of protein disulfide isomerase in a number of disease states small molecule inhibitors of protein disulfide isomerase have been developed These molecules can either target the active site of protein disulfide isomerase irreversibly 18 or reversibly 19 It has been shown that protein disulfide isomerase activity is inhibited by red wine and grape juice which could be the explanation for the French paradox 20 Members EditHuman genes encoding protein disulfide isomerases include 3 21 22 AGR2 AGR3 CASQ1 CASQ2 DNAJC10 ERP27 ERP29 ERP44 P4HB PDIA2 PDIA3 PDIA4 PDIA5 PDIA6 PDIALT TMX1 TMX2 TMX3 TMX4 TXNDC5 TXNDC12References Edit Wilkinson B Gilbert HF June 2004 Protein disulfide isomerase Biochimica et Biophysica Acta 1699 1 2 35 44 doi 10 1016 j bbapap 2004 02 017 PMID 15158710 Gruber CW Cemazar M Heras B Martin JL Craik DJ August 2006 Protein disulfide isomerase the structure of oxidative folding Trends in Biochemical Sciences 31 8 455 64 doi 10 1016 j tibs 2006 06 001 PMID 16815710 a b Galligan JJ Petersen DR July 2012 The human protein disulfide isomerase gene family Human Genomics 6 1 6 doi 10 1186 1479 7364 6 6 PMC 3500226 PMID 23245351 a b c d e f g h i j k Perri ER Thomas CJ Parakh S Spencer DM Atkin JD 2016 The Unfolded Protein Response and the Role of Protein Disulfide Isomerase in Neurodegeneration Frontiers in Cell and Developmental Biology 3 80 doi 10 3389 fcell 2015 00080 PMC 4705227 PMID 26779479 Bechtel TJ Weerapana E March 2017 From structure to redox The diverse functional roles of disulfides and implications in disease Proteomics 17 6 10 1002 pmic 201600391 doi 10 1002 pmic 201600391 PMC 5367942 PMID 28044432 a b c Soares Moretti AI Martins Laurindo FR March 2017 Protein disulfide isomerases Redox connections in and out of the endoplasmic reticulum Archives of Biochemistry and Biophysics The Chemistry of Redox Signaling 617 106 119 doi 10 1016 j abb 2016 11 007 PMID 27889386 Erdogan AJ Riemer J January 2017 Mitochondrial disulfide relay and its substrates mechanisms in health and disease Cell and Tissue Research 367 1 59 72 doi 10 1007 s00441 016 2481 z PMID 27543052 S2CID 35346837 Hu SH Peek JA Rattigan E Taylor RK Martin JL April 1997 Structure of TcpG the DsbA protein folding catalyst from Vibrio cholerae Journal of Molecular Biology 268 1 137 46 doi 10 1006 jmbi 1997 0940 PMID 9149147 Manganas P MacPherson L Tokatlidis K January 2017 Oxidative protein biogenesis and redox regulation in the mitochondrial intermembrane space Cell and Tissue Research 367 1 43 57 doi 10 1007 s00441 016 2488 5 PMC 5203823 PMID 27632163 a b c Oka OB Yeoh HY Bulleid NJ July 2015 Thiol disulfide exchange between the PDI family of oxidoreductases negates the requirement for an oxidase or reductase for each enzyme The Biochemical Journal 469 2 279 88 doi 10 1042 bj20141423 PMC 4613490 PMID 25989104 Hatahet F Ruddock LW October 2007 Substrate recognition by the protein disulfide isomerases The FEBS Journal 274 20 5223 34 doi 10 1111 j 1742 4658 2007 06058 x PMID 17892489 S2CID 9455925 Wittenberg G Danon A 2008 Disulfide bond formation in chloroplasts Plant Science 175 4 459 466 doi 10 1016 j plantsci 2008 05 011 Ryser HJ Fluckiger R August 2005 Progress in targeting HIV 1 entry Drug Discovery Today 10 16 1085 94 doi 10 1016 S1359 6446 05 03550 6 PMID 16182193 a b c McBean GJ Lopez MG Wallner FK June 2017 Redox based therapeutics in neurodegenerative disease British Journal of Pharmacology 174 12 1750 1770 doi 10 1111 bph 13551 PMC 5446580 PMID 27477685 Lundstrom J Holmgren A June 1990 Protein disulfide isomerase is a substrate for thioredoxin reductase and has thioredoxin like activity The Journal of Biological Chemistry 265 16 9114 20 doi 10 1016 S0021 9258 19 38819 2 PMID 2188973 Lyles MM Gilbert HF January 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 doi 10 1021 bi00217a004 PMID 1988050 Raturi A Mutus B July 2007 Characterization of redox state and reductase activity of protein disulfide isomerase under different redox environments using a sensitive fluorescent assay Free Radical Biology amp Medicine 43 1 62 70 doi 10 1016 j freeradbiomed 2007 03 025 PMID 17561094 Hoffstrom BG Kaplan A Letso R Schmid RS Turmel GJ Lo DC Stockwell BR December 2010 Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins Nature Chemical Biology 6 12 900 6 doi 10 1038 nchembio 467 PMC 3018711 PMID 21079601 Kaplan A Gaschler MM Dunn DE Colligan R Brown LM Palmer AG Lo DC Stockwell BR April 2015 Small molecule induced oxidation of protein disulfide isomerase is neuroprotective Proceedings of the National Academy of Sciences of the United States of America 112 17 E2245 52 Bibcode 2015PNAS 112E2245K doi 10 1073 pnas 1500439112 PMC 4418888 PMID 25848045 Galinski CN Zwicker JI Kennedy DR January 2016 Revisiting the mechanistic basis of the French Paradox Red wine inhibits the activity of protein disulfide isomerase in vitro Thrombosis Research 137 169 173 doi 10 1016 j thromres 2015 11 003 PMC 4706467 PMID 26585763 Ellgaard L Ruddock LW January 2005 The human protein disulphide isomerase family substrate interactions and functional properties EMBO Reports 6 1 28 32 doi 10 1038 sj embor 7400311 PMC 1299221 PMID 15643448 Appenzeller Herzog C Ellgaard L April 2008 The human PDI family versatility packed into a single fold Biochimica et Biophysica Acta BBA Molecular Cell Research 1783 4 535 48 doi 10 1016 j bbamcr 2007 11 010 PMID 18093543 External links EditProtein Disulfide Isomerase at the US National Library of Medicine Medical Subject Headings MeSH Portal Biology Retrieved from https en wikipedia org w index php title Protein disulfide isomerase amp oldid 1126864541, wikipedia, wiki, book, books, library,
