Information on EC 1.8.4.2 - protein-disulfide reductase (glutathione)

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The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
1.8.4.2
-
RECOMMENDED NAME
GeneOntology No.
protein-disulfide reductase (glutathione)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 glutathione + protein-disulfide = glutathione-disulfide + protein-dithiol
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glutathione metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
glutathione:protein-disulfide oxidoreductase
Reduces insulin and some other proteins.
CAS REGISTRY NUMBER
COMMENTARY hide
9082-53-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene bdb
-
-
Manually annotated by BRENDA team
chinese hamster
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
SwissProt
Manually annotated by BRENDA team
DsbA homologous
SwissProt
Manually annotated by BRENDA team
DsbA homologous
SwissProt
Manually annotated by BRENDA team
DsbA homologous
SwissProt
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
SwissProt
Manually annotated by BRENDA team
DsbA homologous
SwissProt
Manually annotated by BRENDA team
DsbA homologous
GenBank
Manually annotated by BRENDA team
DsbA homologous
GenBank
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
DsbA homologous
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
the enzyme affects multiple phenotypes in Streptococcus gordonii and is required for production of disulfide-bonded proteins like Anti-CR1 scFv
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,3-dimercaptopropanol + protein disulfide
2,3-dimercaptopropanol disulfide + protein-dithiol
show the reaction diagram
2-mercaptoethanol + protein disulfide
2-mercaptoethanol disulfide + protein-dithiol
show the reaction diagram
alpha-lipoate + protein disulfide
?
show the reaction diagram
-
-
-
-
?
cysteamine + protein disulfide
?
show the reaction diagram
dihydrolipoamide + protein disulfide
?
show the reaction diagram
-
-
-
-
?
dihydrolipoate + protein disulfide
?
show the reaction diagram
dihydrolipoic acid + protein disulfide
?
show the reaction diagram
dithiothreitol + protein disulfide
?
show the reaction diagram
GSH + 5,5'-dithiobis(nitrobenzoic acid)
?
show the reaction diagram
-
-
-
-
?
GSH + AtlS
GSSG + ?
show the reaction diagram
-
-
-
-
?
GSH + insulin
GSSG + reduced insulin chain A and B
show the reaction diagram
GSH + oxytoxin
?
show the reaction diagram
GSH + protein disulfide
GSSG + protein-dithiol
show the reaction diagram
GSH + protein-disulfide
GSSG + protein-dithiol
show the reaction diagram
GSH + vasopressin
?
show the reaction diagram
GSH + vasotocin
?
show the reaction diagram
-
-
-
-
?
GSSG + reduced ribonuclease
GSH + oxidized ribonuclease
show the reaction diagram
hydroxyethyl disulfide + protein disulfide
?
show the reaction diagram
-
-
-
-
?
L-cysteine + protein disulfide
cystine + protein-dithiol
show the reaction diagram
thioglycolic acid + protein disulfide
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GSH + AtlS
GSSG + ?
show the reaction diagram
-
-
-
-
?
GSH + protein disulfide
GSSG + protein-dithiol
show the reaction diagram
GSH + protein-disulfide
GSSG + protein-dithiol
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cs+
-
0.3 M: activates
Mn2+
-
1 mM: activates
phosphate
-
enhances activity
Zn2+
-
essential for activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-Bis(2-chloroethyl)-1-nitrosourea
Aprotinin
arsenite
bacitracin
cysteine
-
at high concentration
deoxycholate
glucagon
-
-
GSSG
-
product inhibition
guanidinium hydrochloride
-
destroys zinc finger thiols of DnaJ protein
Insulin analogs
-
competitive inhibition of insulin degradation, overview
-
iodoacetamide
-
treatment with thiol prior to incubation with GSH and substrate: no inhibition, preincubation with GSH and thiol reagent: inhibition
iodoacetate
lysolecithin
lysophosphatidylcholine
N-Acetyl-L-tyrosine ethyl ester
-
-
N-ethylmaleimide
-
treatment with thiol prior to incubation with GSH and substrate: no inhibition, preincubation with GSH and thiol reagent: inhibition
Oxytoxin
-
-
Phenylarsine oxide
phosphatidic acid
ribonuclease
-
-
-
S-Sulfonated A-chain or B-chain of insulin
-
product inhibition
-
Scrambled forms of ribonuclease and lysozyme
-
inhibition of insulin degradation
-
selenium oxide
-
-
Triton X-100
-
inhibitory for the solubilized enzyme
Vasopressin
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Chelating agents
cysteine disulfide
-
cysteine residues in the redox active catalytic center are essential for conformation stability
deoxycholate
-
activating the enzyme membrane-bound in the microsomal fraction
histidine
-
activates, activation negated by metal ions
phosphatidylethanolamine
Phospholipids
tellurite
-
2.5 mM
-
Triton X-100
-
activating the enzyme membrane-bound in the microsomal fraction
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2
2-mercaptoethanol
-
-
0.27
cysteine
-
-
0.14
Dihydrolipoamide
-
-
0.2
dihydrolipoate
-
-
0.31 - 1.7
GSH
0.003 - 0.031
Insulin
-
0.13
reduced dithiothreitol
-
-
-
additional information
additional information
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00046 - 0.0006
-
insulin-treated and normal rats
0.00081
-
-
0.0035
-
A549 carcinoma cells, substrates GSH, cystamine or cystine
0.0075
-
A549 carcinoma cells, substrate dithiothreitol
0.01
-
purified enzyme
0.03
-
A549 carcinoma cells, substrate hydroxyethyl disulfide
0.067
-
A549 carcinoma cells, substrate lipoate
6
-
highest activity of all bovine tissues
458
-
purified enzyme
758
-
purified enzyme
3273
-
purified enzyme
6000
-
purified enzyme
16000
-
purified enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8.5
-
-
7.8
-
-
7.9
-
thioredoxin
9
-
DL-dihydrolipoate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2 - 10.2
-
pH 6.2: about 10% of activity maximum, pH 10.2: about 20% of activity maximum
6.2 - 8.4
-
-
6.5 - 8.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
-
activity increases to the 3rd week after anthesis
Manually annotated by BRENDA team
-
DU145 carcinoma
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
of alpha and beta cells of islets of Langerhans
Manually annotated by BRENDA team
-
of acinar cells
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain B / BL21-DE3)
Escherichia coli (strain B / BL21-DE3)
Escherichia coli (strain B / BL21-DE3)
Escherichia coli (strain B / BL21-DE3)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Xylella fastidiosa (strain 9a5c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12000
-
? * 12000, SDS-PAGE
14000
-
2 * 14000, SDS-PAGE
14056
-
2 * 14056, unmodified recombinant WhiB1, MALDI-TOF mass spectrometry
14284
-
2 * 14284, reduced protein after alkylation corresponding to the theoretical mass of the recombinant protein with four iodoacetamide mediated modifications of cysteines, MALDI-TOF mass spectrometry
21100
-
DsbA gene product
25700
-
? * 25700, SDS-PAGE
29000
-
gel filtration
37000
-
gel filtration
41000
-
2 * 41000, SDS-PAGE
50000 - 55000
-
gel filtration
54000
-
amino acid sequence determination
54500
-
x * 54500, calculation from nucleotide sequence
58000
-
gel filtration
62500
-
1 * 62500, SDS-PAGE
63000
-
gel filtration
92000
-
gel filtration
120000
150000 - 200000
-
gel filtration
additional information
-
3 molecular forms: MW 56000 is the major form, MW 51000 is active and only present in spleen, possibly a proteolytic product of 56000 MW protein, MW 67000 is possibly a precursor of 56000 MW protein
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
monomer
trimer
-
enzyme contains 3 amino-terminal residues, therefore might be composed of 3 polypeptide chains or subunits
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
phospholipoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallized at 25°C using the hanging-drop vapour-diffusion method, crystals belong to the space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 90.59, b = 102.43, c = 128.96 A
-
hanging-drop vapour diffusion
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
phosphate buffer, 5 h without loss of activity
65
-
30 min, 90% loss of activity
80
-
30 min, about 60% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dimerization after prolonged storage at -20°C, freeze-thawing or heating at 60°C
-
EDTA 5mM, 37°C, phosphate buffer, total loss of activity within 30-60 min, can partially be prevented by NADPH
-
EDTA stabilizes during purification
GSH, 10 mM, enhances heat stability
-
highly susceptible to proteolytic attack
-
insulin, 0.087 mM, decreases heat stability
-
metal ions required for activity and maintenance of the proper conformation of the enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-25°C, pH 7.5, phosphate buffer, months without loss of activity
-
4°C, 90% of the enzyme is converted from its native form with MW 60000 to a fragment of MW 40000-45000
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion-exchange chromatography (DEAE) and gel filtration (Superdex 75)
-
Ni2+-NTA affinity chromatography
-
nickel-nitrilotriacetic acid column chromatography
-
recombinant enzyme
recombinant enzyme from periplasm
-
recombinant wild-type and mutant enzymes
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
characterization of cDNA for human glutathione-insulin transhydrogenase, amino acid sequence analysis, 94% homology to rat amino acid sequence
enzyme variants
-
expressed in Escherichia coli
-
expressed in Escherichia coli strain BL21(DE3)
-
expressed in Escherichia coli strain D5alpha
-
expressed in Escherichia coli TG1 and Rosetta-gami cells
-
expressed in Escherichia coli XL-1 Blue cells
-
expression from plasmid in bacterial expression system, amino acid analysis
-
expression from plasmid in Escherichia coli into the periplasm
-
expression in Escherichia coli from plasmid
-
overexpressed in Escherichia coli
-
overexpression from plasmid in Bacillus brevis, DNA sequence analysis
-
successfully expressed in Brevibacillus choshinensis extracellularly using the secretion vector pNCMO2, and in Escherichia coli intracellularly with an amino-terminal His-tag. Coexpression of CatA protein with recombinant hEGF in the Brevibacillus choshinensis production system increases the yield of native hEGF
-
systematic gene function analysis programm, expression of diverse constructs in Escherichia coli and Bacillus subtilis
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H33G
-
the mutant shows a loss of the capacity of the protein to isomerize, or shuffle, incorrect disulfides of scrambled RNase A yielding 10% active RNase A only
H32PY34R/Q35L/F36I/E37Y
-
active variant
P31H/H32A/Y34G/Q35L/F36R/E37Y
-
active variant
P31H/H32D/Y34S/Q35E/E37S
-
active variant
P31H/H32T/Y34A/Q35S/F36T/E37R
-
inactive variant
P31K/Y34P/Q35V/F36P/E37T
-
inactive variant
P31R/H32G/Y34N/Q35K/F36L/E37A
-
semi-active variant
P31R/H32I/Y34F/F36V/E37P
-
inactive variant
P31R/H32S/Y34C/Q35T/F36Y/E37R
-
semi-active variant
P31Y/H32E/Y34T/Q35A/F36D/E37H
-
inactive variant
C57S
-
site-directed mutagenesis, reduced activity
C57S/C60S
-
site-directed mutagenesis, no activity
C60S
-
site-directed mutagenesis, no activity
additional information
-
DsbA and DsbB insertion mutants are sensitive to dithiothreitol and benzylpenicillin or Cd2+, Hg2+ and Zn2+, pleitropic phenotype
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
DsbA protein is a target for treatment of pathogenic bacteria
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