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Information on EC 5.3.4.1 - protein disulfide-isomerase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P17967
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5.3.4.1 protein disulfide-isomeraseIUBMB Comments
Needs reducing agents or partly reduced enzyme; the reaction depends on sulfhydryl-disulfide interchange.
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- 5.3.4.1
- collagen
- laminin
- integrins
- endothelial
- actin
- fibrosis
-
adhesive
-
basement
- mesenchymal
- vessel
- fiber
- metastasis
- proteoglycans
- vitronectin
- fibrinogen
- matrices
- nephropathy
- albumin
- gelatin
-
interstitial
-
mesangial
- platelet
- monolayer
- cytoskeleton
- glomerular
- rgd
- vimentin
- e-cadherin
-
cell-cell
- adhesions
- zeta
- myofibroblasts
- willebrand
-
epithelial-mesenchymal
- factor-beta
- fak
- fibrin
- metalloproteinases
-
preterm
-
dish
-
biomaterials
- procollagens
- heparan
-
alpha-smooth
- dermal
- tgf-beta
- plasminogen
-
fibrillar
- drug development
-
heparin-binding
- synthesis
- thrombospondin
- medicine
- industry
- diagnostics
- pharmacology
- biotechnology
- analysis
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
fibronectin, pdi, protein disulfide isomerase, erp57, pdia3, protein disulphide isomerase, cabp1, erp44, disulfide isomerase, erp72, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5'-MD
-
-
-
-
58 kDa glucose regulated protein
-
-
-
-
58 kDa microsomal protein
-
-
-
-
CaBP1
-
-
-
-
CaBP2
-
-
-
-
Cellular thyroid hormone binding protein
-
-
-
-
Disulfide interchange enzyme
-
-
-
-
Disulfide isomerase ER-60
-
-
-
-
DsbA
-
-
-
-
DsbC
-
-
-
-
DsbD
-
-
-
-
endoplasmic reticulum protein EUG1
-
-
-
-
Eps1p
ER58
-
-
-
-
ERp-72 homolog
-
-
-
-
ERp57
-
-
-
-
ERP59
-
-
-
-
ERP60
-
-
-
-
ERp72
-
-
-
-
HIP-70
-
-
-
-
Iodothyronine 5'-monodeiodinase
-
-
-
-
P55
-
-
-
-
P58
-
-
-
-
PDI
PDIp
-
-
-
-
protein disulfide isomerase
Protein disulfide isomerase P5
-
-
-
-
Protein disulfide isomerase-related protein
-
-
-
-
Protein disulphide isomerase
-
-
-
-
Protein ERp-72
-
-
-
-
R-cognin
-
-
-
-
Rearrangease
-
-
-
-
Reduced ribonuclease reactivating enzyme
-
-
-
-
Retina cognin
-
-
-
-
S-S rearrangase
-
-
-
-
Thyroid hormone-binding protein
-
-
-
-
Thyroxine deiodinase
-
-
-
-
additional information
PDI
-
-
-
-
additional information
-
PDI, Eug1p, Mpd1p, Mpd2p, and Eps1p belong to the thioredoxin superfamily
additional information
-
the enzymes yPDI, Mpd1p, Mpd2p, and Eug1p belong to the yeast yPDI enzyme family
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
catalyses the rearrangement of -S-S- bonds in proteins
substrate binding and catalytic mechanism
catalyses the rearrangement of -S-S- bonds in proteins
active site structure
-
catalyses the rearrangement of -S-S- bonds in proteins
active site location, structure, and redox state
-
catalyses the rearrangement of -S-S- bonds in proteins
PDI introduces disulfides into proteins, oxidase activity, and provides quality control by catalyzing the rearrangement of incorrect disulfides, isomerase activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
isomerization
-
-
-
-
intramolecular oxidoreduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
Protein disulfide-isomerase
Needs reducing agents or partly reduced enzyme; the reaction depends on sulfhydryl-disulfide interchange.
CAS REGISTRY NUMBER
COMMENTARY
37318-49-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
folded cholera toxin
unfolded cholera toxin
-
PDI binds in the reduced state to the A chain of cholera toxin, in the oxidized state it releases it, PDI may be involved in the retrograde protein transport into the cytosol
-
?
rhodanese
?
-
prevention of rhodanese degeneration, chaperone activity
-
-
?
ribonuclease
?
-
refolding of ribonuclease, isomerase activity, renaturation of reduced ribonuclease, in presence of GSH and GSSG
-
-
?
RNase
?
-
refolding of RNase, renaturation of reduced and of scrambled RNase with almost equal activity
-
-
?
unfolded bovine pancreatic trypsin inhibitor
refolded bovine pancreatic trypsin inhibitor + oxidized glutathione
-
oxidative refolding of denatured bovine pancreatic trypsin inhibitor
-
?
unfolded lysozyme
refolded lysozyme
-
oxidative refolding of reduced and denatured lysozyme in glutathione redox buffer
-
?
unfolded pro-carboxypeptidase Y
refolded pro-carboxypeptidase Y
-
-
-
?
Proteins
Proteins
-
refolding of scrambled ribonuclease
with correct disulfide bonds
?
Proteins
Proteins
-
native, reduced or with wrong disulfide bonds
with correct disulfide bonds
?
Proteins
Proteins
-
native, reduced or with wrong disulfide bonds
with correct disulfide bonds
?
Proteins
Proteins
-
native, reduced or with wrong disulfide bonds
with correct disulfide bonds
?
Proteins
Proteins
-
native, reduced or with wrong disulfide bonds
with correct disulfide bonds
?
Proteins
Proteins
-
cosubstrate: DTT, 2-mercaptoethanol, GSH, or Cys
with correct disulfide bonds
?
additional information
?
-
structure and mechanism of PDI in disulfide formation and oxidative protein folding, overview
-
-
?
additional information
?
-
-
structure and mechanism of PDI in disulfide formation and oxidative protein folding, overview
-
-
?
additional information
?
-
PDI oxidizes pairs of cysteines to form disulfide bonds and can also shuffle incorrect disulfides into their correct pairings, function and mechanism of PDI, PDI has the ability to catalyze dithiol-disulfide exchange reactions, chaperone activity and propensity to form subunits of multi-enzyme complexes, overview
-
-
?
additional information
?
-
-
PDI oxidizes pairs of cysteines to form disulfide bonds and can also shuffle incorrect disulfides into their correct pairings, function and mechanism of PDI, PDI has the ability to catalyze dithiol-disulfide exchange reactions, chaperone activity and propensity to form subunits of multi-enzyme complexes, overview
-
-
?
additional information
?
-
-
the enzyme has an essential role that is distinct from its function in formation of native disulphides
-
-
?
additional information
?
-
-
essential enzyme for yeast cell growth, both oxidase and isomerase activities are required
-
-
?
additional information
?
-
-
PDI plays a key role in catalyzing the folding of secretory proteins
-
-
?
additional information
?
-
-
regulation of PDI and PDI homologues activities, in vivo isomerase activity depends only on full-length PDI, not on PDI-homologues, modeling of disulfide formation, the enzyme catalyzes disulfide formation and isomerization and acts as a chaperone inhibiting aggregation, enzyme assists in the system of chaperones and folding catalysts to ensure proper connection of disulfides and protein folding without improper interactions
-
-
?
additional information
?
-
-
the enzyme is an essential catalyst of disulfide formation with two cysteines in the active site facilitating thiol-disulfide exchange
-
-
?
additional information
?
-
-
the organism is completely dependent on PDI activity for growth
-
-
?
additional information
?
-
-
all 5 domains of PDI are required for full catalytic activity
-
-
?
additional information
?
-
-
Eug1p, Mpd1p, Mpd2p, and Eps1p partially compensate for PDI, substrate specificity of PDI
-
-
?
additional information
?
-
-
non-active site cysteines form a disulfide bridges which destabilizes the N-terminal active site disulfide rendering it a 18fold better oxidant by this way
-
-
?
additional information
?
-
-
the yPDI enzyme family members Mpd1p, Mpd2p, and Eug1p show high chaperone activity, but low isomerase activity compared to PDI, isomerase activity is assayed using the insulin/glutathione coupled assay, chaperone activity is also measured utilizing mastoparan as substrate
-
-
?
additional information
?
-
-
protein disulfide isomerase has a concentration-dependent chaperone-activity and inhibits the aggregation of rhodanese, which has no disulfide bonds
-
-
?
additional information
?
-
-
interactions between the C-terminal domain of Mnl1p and PDI, which include an intermolecular disulfide bond, are essential for subsequent introduction of a disulfide bond into the mannosidase homology domain of Mnl1p by PDI. This disulfide bond is essential for the ER-associated degradation activity of Mnl1p and in turn stabilizes the prolonged association of PDI with Mnl1p
-
-
?
additional information
?
-
-
PDI first recognizes the C-terminal domain of Mnl1p containing Asp607, Glu627, and Trp636 , PDI forms an intermolecular disulfide bond with C5 or C6 of Mnl1p. PDI introduces a disulfide bond between C1 and C3 in the MHDof Mnl1p, the disulfide bond between C1 and C3 in turn stabilizes association of PDI with Mnl1p, and the intermolecular disulfide bond between PDI and C5 or C6 of Mnl1p is partially reduced,whereas maintaining association of PDI and Mnl1p
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
structure and mechanism of PDI in disulfide formation and oxidative protein folding, overview
-
-
?
additional information
?
-
-
structure and mechanism of PDI in disulfide formation and oxidative protein folding, overview
-
-
?
additional information
?
-
-
the enzyme has an essential role that is distinct from its function in formation of native disulphides
-
-
?
additional information
?
-
-
essential enzyme for yeast cell growth, both oxidase and isomerase activities are required
-
-
?
additional information
?
-
-
PDI plays a key role in catalyzing the folding of secretory proteins
-
-
?
additional information
?
-
-
regulation of PDI and PDI homologues activities, in vivo isomerase activity depends only on full-length PDI, not on PDI-homologues, modeling of disulfide formation, the enzyme catalyzes disulfide formation and isomerization and acts as a chaperone inhibiting aggregation, enzyme assists in the system of chaperones and folding catalysts to ensure proper connection of disulfides and protein folding without improper interactions
-
-
?
additional information
?
-
-
the enzyme is an essential catalyst of disulfide formation with two cysteines in the active site facilitating thiol-disulfide exchange
-
-
?
additional information
?
-
-
the organism is completely dependent on PDI activity for growth
-
-
?
additional information
?
-
-
interactions between the C-terminal domain of Mnl1p and PDI, which include an intermolecular disulfide bond, are essential for subsequent introduction of a disulfide bond into the mannosidase homology domain of Mnl1p by PDI. This disulfide bond is essential for the ER-associated degradation activity of Mnl1p and in turn stabilizes the prolonged association of PDI with Mnl1p
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
glutathione is used in vitro as redox system
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
PDI1 gene expression is stress-induced by over 2.5fold in response to e.g. reducing agents such as DTT, or to thiol-specific oxidizing agents such as diamide, other PDI gene homologues are also stress-induced
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
redox equilibrium measurements of wild-type and mutant C90A/C97A enzymes, determination of oxidase and isomerase activities
-
0.002
ribonuclease
-
dithiothreitol, with scrambled ribonuclease as substrate
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 9
-
pH 7.5: about 20% of maximal activity, pH 9.0: about 80% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
-
enzyme exists as an interconvertible mixture of monomers and dimers
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
the close interdependence between Mnl1p and PDI suggests that these two proteins form a functional unit in the ER-associated degradation, ERAD, pathway
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
additional information
-
domain arrangement: two catalytically inactive thioredoxin domains inserted between two catalytically active thioredoxin domains and an acidic C-terminal tail, the four thioredoxin domains form the shape of a twisted U with the active sites facing each other across the long sides, the inside surface is enriched in hydrophobic residues facilitating interactions with misfolded proteins, all 5 domains of PDI are required for full catalytic activity
additional information
-
non-active site cysteines form a disulfide bridge that is stable even under very reducing environment destabilizing the N-terminal active site disulfide which becomes a 18fold better oxidant by this way
additional information
-
PDI domain organization, Eug1p, Mpd1p, Mpd2p, and Eps1p have only one catalytic domain with 2 cysteines, overview
additional information
-
the catalytic domains a and a' are responsible for the oxidase and the isomerase activity, respectively
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
the enzyme has 5 N-glycosylation sites all modified in vivo
glycoprotein
-
expression in Bombyx mori results in production of mostly non-N-glycosylated and some N-glycosylated recombinant protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 24% (w/v) PEG 4000, 100 mM sodium acetate, pH 6.4, 25 mM sodium citrate, pH 6.4, and 17% (v/v) glycerol
purified recombinant residues 23-522 of PDI1, X-ray diffraction structure determination and analysis at 2.4 A resolution, modeling
-
to 3.7 A resolution. PDI is a highly flexible molecule with its catalytic domains, a and a', representing two mobile arms connected to a more rigid core composed of the b and b' domains. The linker between the a domain and the core is more susceptible to degradation than that connecting the a' domain to the core. Molecular flexibility is essential for the enzymatic activity in vitro and in vivo
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C409A
-
site-directed mutagenesis, mutation of the second cysteine of the active site, the mutant shows similar activity to the wild-type enzyme
C64A
-
site-directed mutagenesis, mutation of the second cysteine of the active site, the mutant shows similar activity to the wild-type enzyme
C90A
-
site-directed mutagenesis, mutation of a non-active site cysteine residue, reduced oxidase and isomerase activities compared to the wild-type enzyme
C90A/C97A
-
site-directed mutagenesis, mutation of both non-active site cysteine residues, 60% and 80% reduced oxidase and isomerase activities, respectively, compared to the wild-type enzyme
C97A
-
site-directed mutagenesis, mutation of a non-active site cysteine residue, reduced oxidase and isomerase activities compared to the wild-type enzyme
additional information
additional information
-
a domain a'-deletion mutant shows reduced activity in refolding of RNase compared to the wild-type enzyme
additional information
-
construction of a mutant PDI defective in the a' domain, which bears the isomerase activity, a PDI deletion yeast mutant cannot be rescued by the rat PDI
additional information
-
PDI can rescue a PDI-deficient mutant strain as well as mutants deficient in PDI homologues Eug1p, Mpd1p, Mpd2p, and Eps1p
additional information
-
the PDI1 disruption mutant strain cannot be rescued by chromosomal insertion of the human PDI gene, the human enzyme is not functionally equivalent to the yeast enzyme, tetrad analysis, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain AD494(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type PDI and mutant PDI defective in the a' domain from Escherichia coli by nickel affnity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His-tagged enzyme in Escherichia coli strain AD494(DE3)
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of His-tagged wild-type PDI and mutant PDI defective in the a' domain, which bears the isomerase activity, in Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Webster, P.A.; Pioli, D.; Tuite, M.F.; Freedman, R.B.
Properties and cellular functions of related yeast ER proteins protein disulphide-isomerase and Eug1p
Biochem. Soc. Trans.
23
66S
1995
Saccharomyces cerevisiae
Gilbert, H.F.
Protein disulfide isomerase
Methods Enzymol.
290
26-50
1998
Bos taurus, Saccharomyces cerevisiae, Mammalia, Rattus norvegicus
Mizunaga, T.; Katakura, Y.; Miura, T.; Maruyama, Y.
Purification and characterization of yeast protein disulfide isomerase
J. Biochem.
108
846-851
1990
Bos taurus, Saccharomyces cerevisiae
Noiva, R.
Enzymatic catalysis of disulfide formation
Protein Expr. Purif.
5
1-13
1994
Bacteria, Saccharomyces cerevisiae, eukaryota, Rattus norvegicus
Freeman, R.B.; Hirst, T.R.; Tuite, M.F.
Protein disulphide isomerase: building bridges in protein folding
Trends Biochem. Sci.
19
331-336
1994
Bacteria, Bos taurus, Saccharomyces cerevisiae, Gallus gallus, Oryctolagus cuniculus, eukaryota, Homo sapiens, Rattus norvegicus, Trypanosoma brucei
Katiyar, S.; Till, E.A.; Lennarz, W.J.
Studies on the function of yeast protein disulfide isomerase in renaturation of proteins
Biochim. Biophys. Acta
1548
47-56
2001
Saccharomyces cerevisiae
Tsai, B.; Rodighiero, C.; Lencer, W.I.; Rapoport, T.A.
Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin
Cell
104
937-948
2001
Saccharomyces cerevisiae
Westphal, V.; Darby, N.J.; Winther, J.R.
Functional properties of the two redox-active sites in yeast protein disulfide isomerase in vitro and in vivo
J. Mol. Biol.
286
1229-1239
1999
Saccharomyces cerevisiae
Kimura, T.; Hosoda, Y.; Kitamura, Y.; Nakamura, H.; Horibe, T.; Kikuchi, M.
Functional differences between human and yeast protein disulfide isomerase family proteins
Biochem. Biophys. Res. Commun.
320
359-365
2004
Saccharomyces cerevisiae, Homo sapiens, Saccharomyces cerevisiae trg1/TRG1
Wilkinson, B.; Gilbert, H.F.
Protein disulfide isomerase
Biochim. Biophys. Acta
1699
35-44
2004
Bos taurus, Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Rattus norvegicus
Tian, G.; Xiang, S.; Noiva, R.; Lennarz, W.J.; Schindelin, H.
The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites
Cell
124
61-73
2006
Saccharomyces cerevisiae
Xiao, R.; Wilkinson, B.; Solovyov, A.; Winther, J.R.; Holmgren, A.; Lundstrom-Ljung, J.; Gilbert, H.F.
The contributions of protein disulfide isomerase and its homologues to oxidative protein folding in the yeast endoplasmic reticulum
J. Biol. Chem.
279
49780-49786
2004
Saccharomyces cerevisiae
Wilkinson, B.; Xiao, R.; Gilbert, H.F.
A structural disulfide of yeast protein-disulfide isomerase destabilizes the active site disulfide of the N-terminal thioredoxin domain
J. Biol. Chem.
280
11483-11487
2005
Saccharomyces cerevisiae
Gruber, C.W.; Cemazar, M.; Heras, B.; Martin, J.L.; Craik, D.J.
Protein disulfide isomerase: the structure of oxidative folding
Trends Biochem. Sci.
31
455-464
2006
Arabidopsis thaliana, Chlamydomonas reinhardtii, Escherichia coli, Homo sapiens (P07237), Saccharomyces cerevisiae (P17967), Saccharomyces cerevisiae
Wang, L.; Shimizu, Y.; Mizunaga, T.; Matsumoto, S.; Otsuka, Y.
Expression, purification and characterization of yeast protein disulfide isomerase produced by a recombinant baculovirus-mediated silkworm, Bombyx mori, pupae expression system
Biotechnol. Lett.
30
625-630
2008
Saccharomyces cerevisiae
Tian, G.; Kober, F.X.; Lewandrowski, U.; Sickmann, A.; Lennarz, W.J.; Schindelin, H.
The catalytic activity of protein-disulfide isomerase requires a conformationally flexible molecule
J. Biol. Chem.
283
33630-33640
2008
Saccharomyces cerevisiae
Sakoh-Nakatogawa, M.; Nishikawa, S.; Endo, T.
Roles of protein-disulfide isomerase-mediated disulfide bond formation of yeast Mnl1p in endoplasmic reticulum-associated degradation
J. Biol. Chem.
284
11815-11825
2009
Saccharomyces cerevisiae
Biran, S.; Gat, Y.; Fass, D.
The Eps1p protein disulfide isomerase conserves classic thioredoxin superfamily amino acid motifs but not their functional geometries
PLoS ONE
9
e113431
2014
Saccharomyces cerevisiae (C7GJH6), Saccharomyces cerevisiae, Naumovozyma dairenensis (G0W5T0), Naumovozyma dairenensis CBS-421 (G0W5T0), Saccharomyces cerevisiae JAY291 (C7GJH6)
EXTERNAL LINKS (specific for EC-Number 5.3.4.1)
Transporter Classification Database (TCDB): 8.A.88.2.3, 8.A.88.2.7
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