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Information on EC 5.3.4.1 - protein disulfide-isomerase and Organism(s) Homo sapiens and UniProt Accession Q13087

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     5 Isomerases
         5.3 Intramolecular oxidoreductases
             5.3.4 Transposing S-S bonds
                5.3.4.1 protein disulfide-isomerase
IUBMB Comments
Needs reducing agents or partly reduced enzyme; the reaction depends on sulfhydryl-disulfide interchange.
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: Q13087
Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The taxonomic range for the selected organisms is: Homo sapiens
Reaction Schemes
catalyses the rearrangement of -S-S- bonds in proteins
Synonyms
5'-MD, 58 kDa glucose regulated protein, 58 kDa microsomal protein, AGR2, anterior gradient homolog 2, BPA-binding protein, CaBP1, CaBP2, Cellular thyroid hormone binding protein, cotyledon-specific chloroplast biogenesis factor CYO1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5'-MD
-
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58 kDa glucose regulated protein
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58 kDa microsomal protein
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-
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AGR2
247
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CaBP1
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CaBP2
Cellular thyroid hormone binding protein
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Disulfide interchange enzyme
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Disulfide isomerase ER-60
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DsbA
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DsbC
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DsbD
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Endoplasmic reticulum protein EUG1
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ER protein 57
247
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ER58
-
-
-
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ER60
247
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ERcalcistorin/protein-disulfide isomerase
247
i.e. ECaSt/PDI
ERdj5
247
-
Ero1
247
-
ERP-57
247
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ERp-72 homolog
-
-
-
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ERp18
247
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ERp27
Erp46
ERp57
ERP59
-
-
-
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ERP60
-
-
-
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ERp72
fibronectin
247
extracellular matrix protein fibronectin contains an intrinsic protein-disulfide isomerase activity
HIP-70
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Iodothyronine 5'-monodeiodinase
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multifunctional protein disulfide isomerase
283198, 283199, 283200, 283221
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P55
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P58
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pancreas-specific protein disulfide isomerase
PDI A4
283200
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PDI I
247
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PDI II
247
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PDIA1
PDIA2
283199
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PDIA3
247
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PDIA4
283200
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PDIr
247
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protein disulfide isomerase
protein disulfide isomerase A1
247
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protein disulfide isomerase A5
301249
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Protein disulfide isomerase P5
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Protein disulfide isomerase-related protein
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Protein disulphide isomerase
Protein ERp-72
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protein-disulfide isomerase
247
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R-cognin
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Rearrangease
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Reduced ribonuclease reactivating enzyme
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Retina cognin
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S-S rearrangase
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Thyroid hormone-binding protein
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Thyroxine deiodinase
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-
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TXNDC5
301249
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
catalyses the rearrangement of -S-S- bonds in proteins
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
intramolecular oxidoreduction
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-
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isomerization
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-
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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 hide
37318-49-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
apolipoprotein B
?
show the reaction diagram
-
-
-
-
?
beta-actin
?
show the reaction diagram
-
-
-
-
?
bovine pancreatic trypsin inhibitor
?
show the reaction diagram
-
-
-
-
?
creatine kinase
?
show the reaction diagram
-
refolding of creatine kinase, creatine kinase substrate is denatured by 3 M guanidine-HCl, catalysis of creatine kinase refolding by PDI involves disulfide cross-link and dimer to tetramer switch, PDI suppresses aggregation of denatured inactive casein kinase
-
-
?
D-glyceraldehyde 3-phosphate dehydrogenase
?
show the reaction diagram
-
-
-
-
?
denatured D-glyceraldehyde-3-phosphate dehydrogenase
refolded D-glyceraldehyde-3-phosphate dehydrogenase
show the reaction diagram
-
chaperone activity of PDI
-
?
denatured rhodanese
?
show the reaction diagram
-
PDI exhibits chaperone activity with rhodanese
-
-
?
dieosin glutathione disulfide
eosin glutathione sulfide
show the reaction diagram
-
-
-
-
?
E2A homodimer
E2A-basic helix-loop-helix protein heterodimer
show the reaction diagram
-
PDI I and PDI II foster heterodimer formation between E proteins, i.e. basic-loop-helix proteins of the E2A gene products, by a redox mechanism
-
?
envelope glycoprotein 120
envelope glycoprotein 120
show the reaction diagram
-
i.e. human immunodeficiency virus gp120
-
?
estrogen receptor alpha
?
show the reaction diagram
glutathione disulfide
glutathione
show the reaction diagram
-
-
-
-
?
insulin
?
show the reaction diagram
insulin
reduced insulin
show the reaction diagram
-
-
-
-
?
Insulin-(SS) + GSH
Insulin-(SH)2 + GSSG
show the reaction diagram
integrin alphaIIbbeta3
?
show the reaction diagram
-
-
-
-
?
integrin alphaMb2
?
show the reaction diagram
-
-
-
-
?
integrin alphaVb3
?
show the reaction diagram
-
-
-
-
?
integrin alphaVbeta3
?
show the reaction diagram
-
-
-
-
?
integrin subunit alpha11
?
show the reaction diagram
-
the enzyme activates integrin subunit alpha11
-
-
?
integrin subunit beta1
?
show the reaction diagram
-
the enzyme activates integrin subunit beta1
-
-
?
lactate dehydrogenase
?
show the reaction diagram
-
reactivation of self-aggregated denatured lactate dehydrogenase, guanidine HCl-denatured LDH, chaperone activity, both recombinant wild-type PDI and mutant abb'a' interact with self-aggregated lactate dehydrogenase enhancing LDH reactivation and reducing aggregation
-
-
?
NRCSQGSCWN
NRCSQGSCWN
show the reaction diagram
procollagen I
?
show the reaction diagram
-
-
-
-
?
procollagen III
?
show the reaction diagram
-
-
-
-
?
protein-(SSG)2n
protein(SS)n + n(GSSG)
show the reaction diagram
-
-
-
-
?
Proteins
?
show the reaction diagram
Proteins
Proteins
show the reaction diagram
reduced Ero1alpha
oxidized Ero1alpha
show the reaction diagram
-
-
-
-
?
reduced glutathione peroxidase 7
oxidized glutathione peroxidase 7
show the reaction diagram
-
-
-
-
?
reduced glutathione peroxidase 8
oxidized glutathione peroxidase 8
show the reaction diagram
-
-
-
-
?
rhodanese
?
show the reaction diagram
-
chaperone activity
-
-
?
riboflavin binding protein
?
show the reaction diagram
-
protein disulfide isomerase and quiescin-sulfhydryl oxidase cooperate in vitro to generate native pairings in substrates ribonuclease A, with four disulfide bonds and 105 disulfide isomers of the fully oxidized protein, and avian riboflavin binding protein, with nine disulfide bonds and more than 34 million corresponding disulfide pairings. The isomerase is not a significant substrate of quiescin-sulfhydryl oxidase. Both reduced RNase and riboflavin binding protein can be efficiently refolded in an aerobic solution containing micromolar concentrations of reduced PDI and nanomolar levels of quiescin-sulfhydryl oxidase without any added oxidized PDI or glutathione redox buffer. In the absence of either quiescin-sulfhydryl oxidase or redox buffer, the fastest refolding of riboflavin binding protein is accomplished with excess reduced PDI and just enough oxidized PDI to generate nine disulfides in the protein client
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-
?
ribonuclease A
?
show the reaction diagram
-
protein disulfide isomerase and quiescin-sulfhydryl oxidase cooperate in vitro to generate native pairings in ribonuclease A, with four disulfide bonds and 105 disulfide isomers of the fully oxidized protein, and avian riboflavin binding protein, with nine disulfide bonds and more than 34 million corresponding disulfide pairings. The isomerase is not a significant substrate of quiescin-sulfhydryl oxidase. Both reduced RNase and riboflavin binding protein can be efficiently refolded in an aerobic solution containing micromolar concentrations of reduced PDI and nanomolar levels of quiescin-sulfhydryl oxidase without any added oxidized PDI or glutathione redox buffer
-
-
?
ribonuclease T1
?
show the reaction diagram
-
-
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-
?
RNase A
?
show the reaction diagram
RNase B
?
show the reaction diagram
the ability of the ERp57-calnexin complex to mediate folding of 3H-labeled RNase B is completely dependent on a functional interaction between ERp57 and calnexin, overview
-
-
?
tachyplesin I
?
show the reaction diagram
-
-
-
-
?
thrombospondin-1 + alpha-thrombin + antithrombin III
thrombospondin-1-S-S-alpha-thrombin-S-S-antithrombin III
show the reaction diagram
-
PDI catalyzes formation of disulfide linked complexes of thrombospondin
-
?
tissue factor
?
show the reaction diagram
transforming growth factor-beta1
?
show the reaction diagram
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-
-
-
?
unfolded bovine pancreatic trypsin inhibitor
refolded bovine pancreatic trypsin inhibitor
show the reaction diagram
-
-
-
?
unfolded disulfide-bonded protein
refolded disulfide-bonded protein
show the reaction diagram
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-
-
?
unfolded insulin + reduced glutathione
refolded insulin + oxidized glutathione
show the reaction diagram
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-
-
?
unfolded proinsulin
refolded proinsulin
show the reaction diagram
-
PDI acts both as a chaperone and as an isomerase during folding and disulfid bond formation of proinsulin, chaperone and isomerization activity is required at the beginning of proinsulin folding, the late refolding process only depends on the isomerase activity
-
?
unfolded RNase
refolded RNase
show the reaction diagram
unfolded RNase A
refolded RNase A
show the reaction diagram
unfolded rRNaSe
refolded rRNase
show the reaction diagram
-
refolding of reduced rRNaSe
-
?
vitronectin + thrombin + antithrombin
vitronectin-thrombin-antithrombin
show the reaction diagram
-
PDI catalyzes the formation of disulfide-linked complexes of vitronectin with thrombin-antithrombin
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
beta-actin
?
show the reaction diagram
-
-
-
-
?
E2A homodimer
E2A-basic helix-loop-helix protein heterodimer
show the reaction diagram
-
PDI I and PDI II foster heterodimer formation between E proteins, i.e. basic-loop-helix proteins of the E2A gene products, by a redox mechanism
-
?
estrogen receptor alpha
?
show the reaction diagram
-
i.e. ERalpha, PDI plays a critical role in estrogen responsiveness by functioning as a molecular chaperone and assisting the receptor in differentially regulating target gene expression, PDI alters estrogen-mediated transactivation, overview, PDI enhances ERalpha-DNA interactions in presence of an oxidizing agent
-
-
?
glutathione disulfide
glutathione
show the reaction diagram
-
-
-
-
?
Insulin-(SS) + GSH
Insulin-(SH)2 + GSSG
show the reaction diagram
integrin alphaIIbbeta3
?
show the reaction diagram
-
-
-
-
?
integrin alphaMb2
?
show the reaction diagram
-
-
-
-
?
integrin alphaVb3
?
show the reaction diagram
-
-
-
-
?
integrin alphaVbeta3
?
show the reaction diagram
-
-
-
-
?
integrin subunit alpha11
?
show the reaction diagram
-
the enzyme activates integrin subunit alpha11
-
-
?
integrin subunit beta1
?
show the reaction diagram
-
the enzyme activates integrin subunit beta1
-
-
?
protein-(SSG)2n
protein(SS)n + n(GSSG)
show the reaction diagram
-
-
-
-
?
Proteins
?
show the reaction diagram
tissue factor
?
show the reaction diagram
transforming growth factor-beta1
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
glutathione
thioredoxin
-
the enzymes PDI, P5, ERp72, ERp46 and ERp18 contains a thioredoxin binding site and the CGHC active site
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ag+
-
PDI binds Ag+
Cu+
-
the enzyme can bind 10 Cu+/mol and form a tetramer
Cu2+
-
PDI binds a maximum of 4 mol Cu2+ and is able to reduce it to Cu+, the bound Cu+ is surface-exposed
Mn2+
-
modulates the thiol isomerase activity of protein disulfide isomerase that is bound to integrin alphaVbeta3 and induces its transition to the ligand-competent state
Zn2+
-
Zn2+ induces dimers/oligomers with decreased isomerase activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
iodoacetamide
alkylation of PDIp by iodoacetamide fully abolishes its enzymatic activity while it still retains most of its chaperone activity
12-O-Tetradecanoylphorbol 13-acetate
-
binds to and moderately inhibits PDI
2-(2-carboxy-4-nitro-phenyl) disulfonyl-5-nitrobenzoic acid
-
i.e. NSC517871. Molecular docking simulation into the redox-active site, residues C37, G38, H39, C40. Inhibitor binds to hydrophobic amino acidsA34, W36, C37, C40, H39, T68 and F80. The redox inhibitory conformations are energetically and statistically favored
2-nitro-5-sulfo-sulfonyl-benzoic acid
-
molecular docking simulation into the redox-active site, residues C37, G38, H39, C40. Inhibitor binds to hydrophobic amino acidsA34, W36, C37, C40, H39, T68 and F80. The redox inhibitory conformations are energetically and statistically favored
2-Nitro-5-thiocyanobenzoic acid
-
molecular docking simulation into the redox-active site, residues C37, G38, H39, C40. Inhibitor binds to hydrophobic amino acidsA34, W36, C37, C40, H39, T68 and F80. The redox inhibitory conformations are energetically and statistically favored
3,3',5-triiodo-L-thyronine
3,3',5-triiodothyronine
-
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3,4-dichlorophenol
-
inhibits PDI 3,3',5-triiodo-L-thyronine binding activity
4-nonylphenol
-
inhibits PDI 3,3',5-triiodo-L-thyronine binding activity
4-octylphenol
-
inhibits PDI 3,3',5-triiodo-L-thyronine binding activity
5-(3-carboxy-4-nitro-phenyl) sulfonyl-2-nitrobenzoic acid
-
i.e. NSC695265. Molecular docking simulation into the redox-active site, residues C37, G38, H39, C40. Inhibitor binds to hydrophobic amino acidsA34, W36, C37, C40, H39, T68 and F80. The redox inhibitory conformations are energetically and statistically favored
anti-PDI Fab fragments
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bacitracin
bacitracin A
-
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bisphenol A
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i.e. 2,2-bis(4-hydroxyphenyl)propane, an endocrine disrupting chemical, inhibiting the enzyme's 3,3',5-triiodo-L-thyronine binding activity, its chaperone activity, and its isomerase activity, structural requirements, overview. Inhibits also PDI family members ERp57 and ERp72
CCF642
-
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Dithionitrobenzoic acid
-
molecular docking simulation into the redox-active site, residues C37, G38, H39, C40. Inhibitor binds to hydrophobic amino acidsA34, W36, C37, C40, H39, T68 and F80. The redox inhibitory conformations are energetically and statistically favored
Estrogens
-
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ethyl N-[[[(cyanocarbonyl)(2,4-dimethoxyphenyl)amino]thiophen-2-yl]acetyl]glycinate
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genistein
-
suppresses binding of proinsulin to PDI, inhibits 66% of PDIs chaperone activity
gentamycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
iodoacetamide
-
-
kanamycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
LOC14
-
-
-
MA3 018
-
inhibition of protein disulfide isomerase. Treatment of Mn2+-treated endothelial cells abolishes the conversion of integrin alphaVbeta to the ligand-competent high-affinity state
-
MA3 019
-
inhibition of protein disulfide isomerase. Treatment of Mn2+-treated endothelial cells abolishes the conversion of integrin alphaVbeta to the ligand-competent high-affinity state
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methyl-methanethiosulfonate
-
abolishes PDI oxidoreductase but not chaperone activity
N-ethylmaleimide
-
abolishes PDI oxidoreductase but not chaperone activity
neomycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
paromomycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
Pentachlorophenol
-
inhibits PDI 3,3',5-triiodo-L-thyronine binding activity
phenyl vinyl sulfonate
-
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Phenylarsine oxide
-
complete inhibition at 0.01-0.1 mM in vivo
quercetin 3-rutinoside
-
-
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quercetin-3-rutinoside
-
-
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ribostamycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
S-nitrosocysteine
-
S-nitrosates endogenous or overexpressed PDI in HEK-293T cells
sisomycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
Somatostatin
-
-
streptomycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
tetrabromobisphenyl A
-
TBBPA, inhibits PDI 3,3',5-triiodo-L-thyronine binding activity
tetrachlorobisphenyl A
-
TCBPA, inhibits PDI 3,3',5-triiodo-L-thyronine binding activity
thionitrobenzoic acid
-
molecular docking simulation into the redox-active site, residues C37, G38, H39, C40. Inhibitor binds to hydrophobic amino acidsA34, W36, C37, C40, H39, T68 and F80. The redox inhibitory conformations are energetically and statistically favored
Vancomycin
-
analysis of binding and dissociation constants with PDI and PDI domain deletion mutants
vincristine
-
inhibits chaperone activity but not isomerase activity of both isoforms PDI and P5 in vitro. A 100:1 molar ratio of vincristine to enzyme is sufficient to almost completely inhibit chaperone activity
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
calnexin
interacts with the enzyme via the b and b' domains, binding site and structure, overview
-
DTT
-
absolutely required for activity
additional information
-