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PDBsum entry 1g0t
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* Residue conservation analysis
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Enzyme class:
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E.C.5.3.4.1
- protein disulfide-isomerase.
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Reaction:
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Rearrangement of both intrachain and interchain disulfide bonds in proteins to form the native structures.
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DOI no:
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Nat Struct Biol
7:196-199
(2000)
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PubMed id:
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Crystal structure of the protein disulfide bond isomerase, DsbC, from Escherichia coli.
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A.A.McCarthy,
P.W.Haebel,
A.Törrönen,
V.Rybin,
E.N.Baker,
P.Metcalf.
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ABSTRACT
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DsbC is one of five Escherichia coli proteins required for disulfide bond
formation and is thought to function as a disulfide bond isomerase during
oxidative protein folding in the periplasm. DsbC is a 2 x 23 kDa homodimer and
has both protein disulfide isomerase and chaperone activity. We report the 1.9 A
resolution crystal structure of oxidized DsbC where both Cys-X-X-Cys active
sites form disulfide bonds. The molecule consists of separate thioredoxin-like
domains joined via hinged linker helices to an N-terminal dimerization domain.
The hinges allow relative movement of the active sites, and a broad uncharged
cleft between them may be involved in peptide binding and DsbC foldase
activities.
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Selected figure(s)
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Figure 2.
Figure 2. The hydrophobic cleft. a, Surface representation of
DsbC viewed down the molecular two-fold axis. The broad
uncharged cleft may account for peptide binding and chaperone
activity. Electrostatic surface representations were generated
using GRASP35. Red indicates negative-charged (-13 kT) and blue
positive-charged regions (+13 kT). b, Ribbon diagram shown in
the same orientation.
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Figure 4.
Figure 4. The DsbC active site. a, Stereo view of the final
2F[o]-F[c] electron density map at the active site region of
molecule A in the dimer. The electron density is contoured at
the 1.2  level.
b, Stereo view of hydrogen bond interactions within the active
site shown as dashed lines. Distances for these interactions are
shown in Å. Nitrogen atoms are blue; oxygen atoms are in red;
carbon atoms are in gray; sulfur atoms are in yellow. This
figure was generated using BOBSCRIPT37.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2000,
7,
196-199)
copyright 2000.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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S.R.Shouldice,
B.Heras,
P.M.Walden,
M.Totsika,
M.A.Schembri,
and
J.L.Martin
(2011).
Structure and function of DsbA, a key bacterial oxidative folding catalyst.
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Antioxid Redox Signal,
14,
1729-1760.
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H.Kadokura,
and
J.Beckwith
(2010).
Mechanisms of oxidative protein folding in the bacterial cell envelope.
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Antioxid Redox Signal,
13,
1231-1246.
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J.F.Collet,
and
J.Messens
(2010).
Structure, function, and mechanism of thioredoxin proteins.
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Antioxid Redox Signal,
13,
1205-1216.
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S.R.Shouldice,
S.H.Cho,
D.Boyd,
B.Heras,
M.Eser,
J.Beckwith,
P.Riggs,
J.L.Martin,
and
M.Berkmen
(2010).
In vivo oxidative protein folding can be facilitated by oxidation-reduction cycling.
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Mol Microbiol,
75,
13-28.
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PDB codes:
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B.Heras,
S.R.Shouldice,
M.Totsika,
M.J.Scanlon,
M.A.Schembri,
and
J.L.Martin
(2009).
DSB proteins and bacterial pathogenicity.
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Nat Rev Microbiol,
7,
215-225.
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C.Budiman,
K.Bando,
C.Angkawidjaja,
Y.Koga,
K.Takano,
and
S.Kanaya
(2009).
Engineering of monomeric FK506-binding protein 22 with peptidyl prolyl cis-trans isomerase. Importance of a V-shaped dimeric structure for binding to protein substrate.
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FEBS J,
276,
4091-4101.
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G.Ren,
D.Stephan,
Z.Xu,
Y.Zheng,
D.Tang,
R.S.Harrison,
M.Kurz,
R.Jarrott,
S.R.Shouldice,
A.Hiniker,
J.L.Martin,
B.Heras,
and
J.C.Bardwell
(2009).
Properties of the thioredoxin fold superfamily are modulated by a single amino Acid residue.
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J Biol Chem,
284,
10150-10159.
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PDB code:
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H.Li,
H.Ke,
G.Ren,
X.Qiu,
Y.X.Weng,
and
C.C.Wang
(2009).
Thermal-induced dissociation and unfolding of homodimeric DsbC revealed by temperature-jump time-resolved infrared spectra.
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Biophys J,
97,
2811-2819.
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S.A.Arredondo,
T.F.Chen,
A.F.Riggs,
H.F.Gilbert,
and
G.Georgiou
(2009).
Role of dimerization in the catalytic properties of the Escherichia coli disulfide isomerase DsbC.
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J Biol Chem,
284,
23972-23979.
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B.S.Mamathambika,
and
J.C.Bardwell
(2008).
Disulfide-linked protein folding pathways.
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Annu Rev Cell Dev Biol,
24,
211-235.
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G.Tian,
F.X.Kober,
U.Lewandrowski,
A.Sickmann,
W.J.Lennarz,
and
H.Schindelin
(2008).
The Catalytic Activity of Protein-disulfide Isomerase Requires a Conformationally Flexible Molecule.
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J Biol Chem,
283,
33630-33640.
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PDB code:
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J.L.Pan,
I.Sliskovic,
and
J.C.Bardwell
(2008).
Mutants in DsbB that appear to redirect oxidation through the disulfide isomerization pathway.
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J Mol Biol,
377,
1433-1442.
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S.Arredondo,
L.Segatori,
H.F.Gilbert,
and
G.Georgiou
(2008).
De Novo Design and Evolution of Artificial Disulfide Isomerase Enzymes Analogous to the Bacterial DsbC.
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J Biol Chem,
283,
31469-31476.
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S.Gleiter,
and
J.C.Bardwell
(2008).
Disulfide bond isomerization in prokaryotes.
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Biochim Biophys Acta,
1783,
530-534.
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S.Venketesh,
and
C.Dayananda
(2008).
Properties, potentials, and prospects of antifreeze proteins.
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Crit Rev Biotechnol,
28,
57-82.
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X.Ding,
Z.M.Lv,
Y.Zhao,
H.Min,
and
W.J.Yang
(2008).
MTH1745, a protein disulfide isomerase-like protein from thermophilic archaea, Methanothermobacter thermoautotrophicum involving in stress response.
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Cell Stress Chaperones,
13,
239-246.
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A.M.Åasica,
and
E.K.Jagusztyn-Krynicka
(2007).
The role of Dsb proteins of Gram-negative bacteria in the process of pathogenesis.
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FEMS Microbiol Rev,
31,
626-636.
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B.Heras,
M.Kurz,
S.R.Shouldice,
and
J.L.Martin
(2007).
The name's bond......disulfide bond.
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Curr Opin Struct Biol,
17,
691-698.
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S.M.Yeh,
N.Koon,
C.Squire,
and
P.Metcalf
(2007).
Structures of the dimerization domains of the Escherichia coli disulfide-bond isomerase enzymes DsbC and DsbG.
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Acta Crystallogr D Biol Crystallogr,
63,
465-471.
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PDB codes:
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S.Vucetic,
H.Xie,
L.M.Iakoucheva,
C.J.Oldfield,
A.K.Dunker,
Z.Obradovic,
and
V.N.Uversky
(2007).
Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.
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J Proteome Res,
6,
1899-1916.
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A.Lewin,
A.Crow,
A.Oubrie,
and
N.E.Le Brun
(2006).
Molecular basis for specificity of the extracytoplasmic thioredoxin ResA.
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J Biol Chem,
281,
35467-35477.
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PDB codes:
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C.S.Sevier,
and
C.A.Kaiser
(2006).
Conservation and diversity of the cellular disulfide bond formation pathways.
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Antioxid Redox Signal,
8,
797-811.
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C.W.Gruber,
M.Cemazar,
B.Heras,
J.L.Martin,
and
D.J.Craik
(2006).
Protein disulfide isomerase: the structure of oxidative folding.
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Trends Biochem Sci,
31,
455-464.
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G.Gopalan,
Z.He,
K.P.Battaile,
S.Luan,
and
K.Swaminathan
(2006).
Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana.
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Proteins,
65,
789-795.
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G.Tian,
S.Xiang,
R.Noiva,
W.J.Lennarz,
and
H.Schindelin
(2006).
The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites.
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Cell,
124,
61-73.
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PDB code:
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H.P.Su,
D.Y.Lin,
and
D.N.Garboczi
(2006).
The structure of G4, the poxvirus disulfide oxidoreductase essential for virus maturation and infectivity.
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J Virol,
80,
7706-7713.
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PDB code:
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J.L.Pan,
and
J.C.Bardwell
(2006).
The origami of thioredoxin-like folds.
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Protein Sci,
15,
2217-2227.
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J.Messens,
and
J.F.Collet
(2006).
Pathways of disulfide bond formation in Escherichia coli.
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Int J Biochem Cell Biol,
38,
1050-1062.
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K.Maeda,
P.Hägglund,
C.Finnie,
B.Svensson,
and
A.Henriksen
(2006).
Structural basis for target protein recognition by the protein disulfide reductase thioredoxin.
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Structure,
14,
1701-1710.
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PDB code:
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L.Segatori,
L.Murphy,
S.Arredondo,
H.Kadokura,
H.Gilbert,
J.Beckwith,
and
G.Georgiou
(2006).
Conserved role of the linker alpha-helix of the bacterial disulfide isomerase DsbC in the avoidance of misoxidation by DsbB.
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J Biol Chem,
281,
4911-4919.
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N.Ouyang,
Y.G.Gao,
H.Y.Hu,
and
Z.X.Xia
(2006).
Crystal structures of E. coli CcmG and its mutants reveal key roles of the N-terminal beta-sheet and the fingerprint region.
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Proteins,
65,
1021-1031.
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PDB codes:
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S.J.Li,
X.G.Hong,
Y.Y.Shi,
H.Li,
and
C.C.Wang
(2006).
Annular arrangement and collaborative actions of four domains of protein-disulfide isomerase: a small angle X-ray scattering study in solution.
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J Biol Chem,
281,
6581-6588.
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S.Mkrtchian,
and
T.Sandalova
(2006).
ERp29, an unusual redox-inactive member of the thioredoxin family.
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Antioxid Redox Signal,
8,
325-337.
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H.Kadokura,
L.Nichols,
and
J.Beckwith
(2005).
Mutational alterations of the key cis proline residue that cause accumulation of enzymatic reaction intermediates of DsbA, a member of the thioredoxin superfamily.
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J Bacteriol,
187,
1519-1522.
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M.Berkmen,
D.Boyd,
and
J.Beckwith
(2005).
The nonconsecutive disulfide bond of Escherichia coli phytase (AppA) renders it dependent on the protein-disulfide isomerase, DsbC.
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J Biol Chem,
280,
11387-11394.
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T.C.Elton,
S.J.Holland,
L.S.Frost,
and
B.Hazes
(2005).
F-like type IV secretion systems encode proteins with thioredoxin folds that are putative DsbC homologues.
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J Bacteriol,
187,
8267-8277.
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V.M.Hermann,
J.F.Cutfield,
and
M.J.Hubbard
(2005).
Biophysical characterization of ERp29. Evidence for a key structural role of cysteine 125.
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J Biol Chem,
280,
13529-13537.
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Y.Y.Shi,
X.G.Hong,
and
C.C.Wang
(2005).
The C-terminal (331-376) sequence of Escherichia coli DnaJ is essential for dimerization and chaperone activity: a small angle X-ray scattering study in solution.
|
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J Biol Chem,
280,
22761-22768.
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A.Crow,
R.M.Acheson,
N.E.Le Brun,
and
A.Oubrie
(2004).
Structural basis of Redox-coupled protein substrate selection by the cytochrome c biosynthesis protein ResA.
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J Biol Chem,
279,
23654-23660.
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PDB codes:
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A.Rozhkova,
C.U.Stirnimann,
P.Frei,
U.Grauschopf,
R.Brunisholz,
M.G.Grütter,
G.Capitani,
and
R.Glockshuber
(2004).
Structural basis and kinetics of inter- and intramolecular disulfide exchange in the redox catalyst DsbD.
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EMBO J,
23,
1709-1719.
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PDB codes:
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B.Heras,
M.A.Edeling,
H.J.Schirra,
S.Raina,
and
J.L.Martin
(2004).
Crystal structures of the DsbG disulfide isomerase reveal an unstable disulfide.
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Proc Natl Acad Sci U S A,
101,
8876-8881.
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PDB codes:
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F.Baneyx,
and
M.Mujacic
(2004).
Recombinant protein folding and misfolding in Escherichia coli.
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Nat Biotechnol,
22,
1399-1408.
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J.T.Tan,
and
J.C.Bardwell
(2004).
Key players involved in bacterial disulfide-bond formation.
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Chembiochem,
5,
1479-1487.
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K.Banaszak,
I.Mechin,
G.Frost,
and
W.Rypniewski
(2004).
Structure of the reduced disulfide-bond isomerase DsbC from Escherichia coli.
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Acta Crystallogr D Biol Crystallogr,
60,
1747-1752.
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PDB code:
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K.Ginalski,
L.Kinch,
L.Rychlewski,
and
N.V.Grishin
(2004).
DCC proteins: a novel family of thiol-disulfide oxidoreductases.
|
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Trends Biochem Sci,
29,
339-342.
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L.Segatori,
P.J.Paukstelis,
H.F.Gilbert,
and
G.Georgiou
(2004).
Engineered DsbC chimeras catalyze both protein oxidation and disulfide-bond isomerization in Escherichia coli: Reconciling two competing pathways.
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Proc Natl Acad Sci U S A,
101,
10018-10023.
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M.A.Edeling,
U.Ahuja,
B.Heras,
L.Thöny-Meyer,
and
J.L.Martin
(2004).
The acidic nature of the CcmG redox-active center is important for cytochrome c maturation in Escherichia coli.
|
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J Bacteriol,
186,
4030-4033.
|
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M.Cemazar,
S.Zahariev,
S.Pongor,
and
P.J.Hore
(2004).
Oxidative folding of Amaranthus alpha-amylase inhibitor: disulfide bond formation and conformational folding.
|
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J Biol Chem,
279,
16697-16705.
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M.Miot,
and
J.M.Betton
(2004).
Protein quality control in the bacterial periplasm.
|
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Microb Cell Fact,
3,
4.
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M.Zhang,
A.F.Monzingo,
L.Segatori,
G.Georgiou,
and
J.D.Robertus
(2004).
Structure of DsbC from Haemophilus influenzae.
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Acta Crystallogr D Biol Crystallogr,
60,
1512-1518.
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PDB code:
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E.A.Kersteen,
and
R.T.Raines
(2003).
Catalysis of protein folding by protein disulfide isomerase and small-molecule mimics.
|
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Antioxid Redox Signal,
5,
413-424.
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H.Kadokura,
F.Katzen,
and
J.Beckwith
(2003).
Protein disulfide bond formation in prokaryotes.
|
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Annu Rev Biochem,
72,
111-135.
|
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J.W.Allen,
O.Daltrop,
J.M.Stevens,
and
S.J.Ferguson
(2003).
C-type cytochromes: diverse structures and biogenesis systems pose evolutionary problems.
|
| |
Philos Trans R Soc Lond B Biol Sci,
358,
255-266.
|
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R.Ortenberg,
and
J.Beckwith
(2003).
Functions of thiol-disulfide oxidoreductases in E. coli: redox myths, realities, and practicalities.
|
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Antioxid Redox Signal,
5,
403-411.
|
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Z.Zhao,
Y.Peng,
S.F.Hao,
Z.H.Zeng,
and
C.C.Wang
(2003).
Dimerization by domain hybridization bestows chaperone and isomerase activities.
|
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J Biol Chem,
278,
43292-43298.
|
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E.Gross,
C.S.Sevier,
A.Vala,
C.A.Kaiser,
and
D.Fass
(2002).
A new FAD-binding fold and intersubunit disulfide shuttle in the thiol oxidase Erv2p.
|
| |
Nat Struct Biol,
9,
61-67.
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PDB codes:
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F.Katzen,
M.Deshmukh,
F.Daldal,
and
J.Beckwith
(2002).
Evolutionary domain fusion expanded the substrate specificity of the transmembrane electron transporter DsbD.
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| |
EMBO J,
21,
3960-3969.
|
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H.Kadokura,
and
J.Beckwith
(2002).
Four cysteines of the membrane protein DsbB act in concert to oxidize its substrate DsbA.
|
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EMBO J,
21,
2354-2363.
|
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J.F.Collet,
and
J.C.Bardwell
(2002).
Oxidative protein folding in bacteria.
|
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Mol Microbiol,
44,
1-8.
|
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J.F.Collet,
J.Riemer,
M.W.Bader,
and
J.C.Bardwell
(2002).
Reconstitution of a disulfide isomerization system.
|
| |
J Biol Chem,
277,
26886-26892.
|
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|
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M.A.Edeling,
L.W.Guddat,
R.A.Fabianek,
L.Thöny-Meyer,
and
J.L.Martin
(2002).
Structure of CcmG/DsbE at 1.14 A resolution: high-fidelity reducing activity in an indiscriminately oxidizing environment.
|
| |
Structure,
10,
973-979.
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PDB code:
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P.W.Haebel,
D.Goldstone,
F.Katzen,
J.Beckwith,
and
P.Metcalf
(2002).
The disulfide bond isomerase DsbC is activated by an immunoglobulin-fold thiol oxidoreductase: crystal structure of the DsbC-DsbDalpha complex.
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EMBO J,
21,
4774-4784.
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PDB codes:
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D.Goldstone,
P.W.Haebel,
F.Katzen,
M.W.Bader,
J.C.Bardwell,
J.Beckwith,
and
P.Metcalf
(2001).
DsbC activation by the N-terminal domain of DsbD.
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Proc Natl Acad Sci U S A,
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D.Ritz,
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(2001).
Roles of thiol-redox pathways in bacteria.
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Annu Rev Microbiol,
55,
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E.Liepinsh,
M.Baryshev,
A.Sharipo,
M.Ingelman-Sundberg,
G.Otting,
and
S.Mkrtchian
(2001).
Thioredoxin fold as homodimerization module in the putative chaperone ERp29: NMR structures of the domains and experimental model of the 51 kDa dimer.
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| |
Structure,
9,
457-471.
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PDB codes:
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M.W.Bader,
A.Hiniker,
J.Regeimbal,
D.Goldstone,
P.W.Haebel,
J.Riemer,
P.Metcalf,
and
J.C.Bardwell
(2001).
Turning a disulfide isomerase into an oxidase: DsbC mutants that imitate DsbA.
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Native disulfide bond formation in proteins.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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