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Information on EC 1.8.4.16 - thioredoxin:protein disulfide reductase and Organism(s) Escherichia coli and UniProt Accession P36655
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1.8.4.16 thioredoxin:protein disulfide reductaseIUBMB Comments
DsbD is an inner membrane protein found in Gram-negative bacteria that transfers electrons from cytoplasmic thioredoxin to the periplasmic substrate proteins DsbC, DsbG and CcmG, reducing disulfide bonds in the target proteins to dithiols. DsbD consists of three domains: a periplasmic N-terminal domain, a central transmembrane domain and a periplasmic C-terminal domain.
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Word Map
- 1.8.4.16
- chaperone
- methanothermobacter
-
pdi-like
-
extremophiles
- thermoautotrophicum
- gssg
-
testis-specific
- pdilt
-
mercuric
-
agrobacterium-mediated
-
nipponbare
-
non-protein
- phytochelatins
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non-classical
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
+
=
+
a [protein] with reduced L-cysteine residues
+
=
a [protein] carrying a disulfide bond
+
Synonyms
disulfide isomerase-like protein, disulfide bond reductase, dsbdalpha, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dipZ
DsbD
dipZ
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-
-
-
DsbD
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PATHWAY SOURCE
PATHWAYS
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-, -, -
SYSTEMATIC NAME
IUBMB Comments
thioredoxin:protein disulfide oxidoreductase (dithiol-forming)
DsbD is an inner membrane protein found in Gram-negative bacteria that transfers electrons from cytoplasmic thioredoxin to the periplasmic substrate proteins DsbC, DsbG and CcmG, reducing disulfide bonds in the target proteins to dithiols. DsbD consists of three domains: a periplasmic N-terminal domain, a central transmembrane domain and a periplasmic C-terminal domain.
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
[DsbC protein] carrying a disulfide bond + thioredoxin
[DsbC protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
?
[DsbE protein] carrying a disulfide bond + thioredoxin
[DsbE protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
?
[DsbG protein] carrying a disulfide bond + thioredoxin
[DsbG protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
?
a [protein] carrying a disulfide bond + thioredoxin
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
a [protein] carrying a disulfide bond + thioredoxin-1
a [protein] with reduced L-cysteine residues + thioredoxin-1 disulfide
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overall reaction
-
-
?
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
a [protein] carrying a disulfide bond + thioredoxin
-
overall reaction
-
-
?
insulin + dithiothreitol
reduced insulin + oxidized dithiothreitol
-
-
-
-
?
[CcmG protein] carrying a disulfide bond + thioredoxin
[CcmG protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbC protein] carrying a disulfide bond + thioredoxin
[DsbC protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbC protein] carrying a disulfide bond + thioredoxin
[DsbC] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbC protein] with reduced L-cysteine residues + thioredoxin disulfide
[DsbC protein] carrying a disulfide bond + thioredoxin
-
-
-
-
?
[DsbG protein] carrying a disulfide bond + thioredoxin
[DsbG protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbG protein] with reduced L-cysteine residues + thioredoxin disulfide
[DsbG protein] carrying a disulfide bond + thioredoxin
-
-
-
-
?
a [protein] carrying a disulfide bond + thioredoxin
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
-
overall reaction
-
-
?
a [protein] carrying a disulfide bond + thioredoxin
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
-
overall reaction
?
-
-
additional information
?
-
the enzyme does not catalyze the reduction of the disulfide of the thioredoxin-like oxidant DsbA
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-
-
additional information
?
-
the enzyme transfers reducing power from the cytoplasm to the periplasm so as to facilitate the formation of correct disulphide bonds and c-type cytochromes in the latter compartment
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-
-
additional information
?
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-
electron transfer by the enzyme involves sequential reduction and oxidation of its three structural domains, in which reducing potential is transferred from cytoplasmic thioredoxin to the beta domain, then successively to gamma and alpha, and thence to periplasmic substrates. Formation of a disulfide bond between cysteines 163 and 285 of the beta domain is part of the mechanism of the transmembrane electron transfer by the enzyme
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-
-
additional information
?
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-
the enzyme includes three domains, each containing a pair of cysteine residues that perform a series of disulfide exchange reactions. In the first step, the transmembrane domain accepts electrons from thioredoxin in the cytoplasm; these are then transferred to the periplasmic C-terminal domain and finally to the N-terminal domain, which is also located in the periplasm
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-
-
additional information
?
-
-
the enzyme is composed of three domains, each containing two redox-active cysteines. All six of these cysteines are required for enzyme activity. The N-terminal periplasmic domain DsbDalpha directly reduces DsbC. DsbDalpha is then itself reduced by the C-terminal periplasmic domain, DsbDgamma, a thioredoxin-like polypeptide. The resulting oxidized DsbDgamma is reduced by the membrane-embedded DsbDbeta domain that contains eight transmembrane segments. Electrons passed from cytoplasmic thioredoxin 1 restore DsbDbeta to the reduced form, thus allowing it to continue to transfer electrons to DsbDgamma
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-
-
additional information
?
-
-
the enzyme transports electrons without using a metabolite or a cofactor
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-
-
additional information
?
-
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the periplasmic protein TrbB relies on the enzyme from Escherichia coli for maintenance of its C-X-X-C redox active site motif which is responsible for its enzymatic activity
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-
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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
[DsbC protein] carrying a disulfide bond + thioredoxin
[DsbC protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
?
[DsbE protein] carrying a disulfide bond + thioredoxin
[DsbE protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
?
[DsbG protein] carrying a disulfide bond + thioredoxin
[DsbG protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
?
a [protein] carrying a disulfide bond + thioredoxin
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
a [protein] carrying a disulfide bond + thioredoxin-1
a [protein] with reduced L-cysteine residues + thioredoxin-1 disulfide
-
overall reaction
-
-
?
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
a [protein] carrying a disulfide bond + thioredoxin
-
overall reaction
-
-
?
[CcmG protein] carrying a disulfide bond + thioredoxin
[CcmG protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbC protein] carrying a disulfide bond + thioredoxin
[DsbC protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbC protein] carrying a disulfide bond + thioredoxin
[DsbC] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbC protein] with reduced L-cysteine residues + thioredoxin disulfide
[DsbC protein] carrying a disulfide bond + thioredoxin
-
-
-
-
?
[DsbG protein] carrying a disulfide bond + thioredoxin
[DsbG protein] with reduced L-cysteine residues + thioredoxin disulfide
-
-
-
-
?
[DsbG protein] with reduced L-cysteine residues + thioredoxin disulfide
[DsbG protein] carrying a disulfide bond + thioredoxin
-
-
-
-
?
a [protein] carrying a disulfide bond + thioredoxin
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
-
overall reaction
-
-
?
a [protein] carrying a disulfide bond + thioredoxin
a [protein] with reduced L-cysteine residues + thioredoxin disulfide
-
overall reaction
?
-
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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enzyme loss leads to hypersensitivity to dithiothreitol and benzylpenicillin
metabolism
physiological function
metabolism
-
cytoplasmic electrons donated by thioredoxin are transferred into the periplasm via the enzyme
metabolism
-
the enzyme accepts electrons from cytoplasmic thioredoxin and shuttles these electrons via a well-defined cascade through the membrane-spanning region and into the periplasm
metabolism
-
the enzyme generates a reducing source in the periplasm, which is required for maintaining proper redox conditions
metabolism
-
the enzyme is required to maintain the functional oxidation state of DsbC and DsbG
metabolism
-
the enzyme mediates electron transfer from the cytoplasm across the membrane
metabolism
-
the enzyme transfers reducing potential to periplasmic protein disulfide bond isomerases and to the cytochromexa0c thioreduction pathway
physiological function
-
overproduction of the enzyme and protein disulfide isomerase DsbC markedly enhances periplasmic production of human nerve growth factor in Escherichia coli
physiological function
-
the enzyme is essential for bacterial growth at temperatures above 42°C
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
using 25% (w/v) poly(ethylene glycol) 4000, 0.1 M sodium acetate, pH 4.6, and 0.2 M NH4SO4
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C103A/C109A
Echerichia coli expressing the C103A and C109A mutations is Cu2+ sensitive and shows no enzymatic activity
C163A/C282A
Echerichia coli expressing the C163A and C282A mutations is Cu2+ resistant
C163A/C285A
Echerichia coli expressing the C163A and C285A mutations is Cu2+ sensitive and shows no enzymatic activity
C282A/C285A
Echerichia coli expressing the C282A and C285A mutations is Cu2+ resistant
C461A/C464A
Echerichia coli expressing the C461A and C464A mutations is Cu2+ sensitive
C103A
C464A
D455N/E468Q
-
in the double mutant of periplasmic C-terminal domain of the enzyme, the pK(a) value of Cys461 is lowered to 8.6, a value close to that expected for an unperturbed cysteine residue
P162A
-
the mutation leads to less viability on copper and less susceptibility to air oxidation than wild type
P166A
-
the mutation leads to less viability on copper and less susceptibility to air oxidation than wild type
P284A
-
the mutation leads to less viability on copper and less susceptibility to air oxidation than wild type
P289A
-
the mutation leads to less viability on copper and less susceptibility to air oxidation than wild type
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-Sepharose column chromatography, HiTrap chelating column chromatography, and DEAE-Sepharose column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transcription of the enzyme gene is decreased at 50°C, but not completely turned off
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Goulding, C.; Sawaya, M.; Parseghian, A.; Lim, V.; Eisenberg, D.; Missiakas, D.
Thiol-disulfide exchange in an immunoglobulin-like fold Structure of the N-terminal domain of DsbD
Biochemistry
41
6920-6927
2002
Escherichia coli (P36655)
Mavridou, D.; Stelzl, L.; Ferguson, S.; Redfield, C.
1H, 13C and 15N resonance assignments for the oxidized and reduced states of the N-terminal domain of DsbD from Escherichia coli
Biomol. NMR Assign.
6
163-167
2012
Escherichia coli
Katzen, F.; Beckwith, J.
Transmembrane electron transfer by the membrane protein DsbD occurs via a disulfide bond cascade
Cell
103
769-779
2000
Escherichia coli
Missiakas, D.; Schwager, F.; Raina, S.
Identification and charactcerization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli
EMBO J.
14
3415-3424
1995
Escherichia coli
Stewart, E.; Katzen, F.; Beckwith, J.
Six conserved cysteines of the membrane protein DsbD are required for the transfer of electrons from the cytoplasm to the periplasm of Escherichia coli
EMBO J.
18
5963-5971
1999
Escherichia coli
Katzen, F.; Deshmukh, M.; Daldal, F.; Beckwith, J.
Evolutionary domain fusion expanded the substrate specificity of the transmembrane electron transporter DsbD
EMBO J.
21
3960-3969
2002
Escherichia coli, Rhodobacter capsulatus
Cho, S.; Porat, A.; Ye, J.; Beckwith, J.
Redox-active cysteines of a membrane electron transporter DsbD show dual compartment accessibility
EMBO J.
26
3509-3520
2007
Escherichia coli
Hiniker, A.; Vertommen, D.; Bardwell, J.; Collet, J.
Evidence for conformational changes within DsbD Possible role for membrane-embedded proline residues
J. Bacteriol.
188
7317-7320
2006
Escherichia coli
Hemmis, C.; Berkmen, M.; Eser, M.; Schildbach, J.
TrbB from conjugative plasmid F is a structurally distinct disulfide isomerase that requires DsbD for redox state maintenance
J. Bacteriol.
193
4588-4597
2011
Escherichia coli
Kurokawa, Y.; Yanagi, H.; Yura, T.
Overproduction of bacterial protein disulfide isomerase (DsbC) and its modulator (DsbD) markedly enhances periplasmic production of human nerve growth factor in Escherichia coli
J. Biol. Chem.
276
14393-14399
2001
Escherichia coli
-
Krupp, R.; Chan, C.; Missiakas, D.
DsbD-catalyzed transport of electrons across the membrane of Escherichia coli
J. Biol. Chem.
276
3696-3701
2001
Escherichia coli
Cho, S.; Beckwith, J.
Two snapshots of electron transport across the membrane Insights into the structure and function of DsbD
J. Biol. Chem.
284
11416-11424
2009
Escherichia coli
Mavridou, D.; Stevens, J.; Goddard, A.; Willis, A.; Ferguson, S.; Redfield, C.
Control of periplasmic interdomain thiol disulfide exchange in the transmembrane oxidoreductase DsbD
J. Biol. Chem.
284
3219-3226
2009
Escherichia coli
Mavridou, D.; Stevens, J.; Ferguson, S.; Redfield, C.
Active-site properties of the oxidized and reduced C-terminal domain of DsbD obtained by NMR spectroscopy
J. Mol. Biol.
370
643-658
2007
Escherichia coli
Chung, J.; Chen, T.; Missiakas, D.
Transfer of electrons across the cytoplasmic membrane by DsbD, a membrane protein involved in thiol-disulphide exchange and protein folding in the bacterial periplasm
Mol. Microbiol.
35
1099-1109
2000
Escherichia coli
Gordon, E.; Page, M.; Willis, A.; Ferguson, S.
Escherichia coli DipZ Anatomy of a transmembrane protein disulphide reductase in which three pairs of cysteine residues, one in each of three domains, contribute differentially to function
Mol. Microbiol.
35
1360-1374
2000
Escherichia coli (P36655)
Katzen, F.; Beckwith, J.
Role and location of the unusual redox-active cysteines in the hydrophobic domain of the transmembrane electron transporter DsbD
Proc. Natl. Acad. Sci. USA
100
10471-10476
2003
Escherichia coli
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