Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: protein disulfide isomerase/protein disulfide oxidoreductase - DsbCreduced



Gene: dsbC Accession Numbers: EG11070 (EcoCyc), b2893, ECK2888

Synonyms: xprA, DsbCreduced, disulfide oxidoreductase 2

Regulation Summary Diagram: ?

Subunit composition of protein disulfide isomerase/protein disulfide oxidoreductase - DsbCreduced = [DsbC]2
         DsbC monomer = DsbC

Alternative forms of protein disulfide isomerase/protein disulfide oxidoreductase - DsbCreduced: protein disulfide isomerase/protein disulfide oxidoreductase - DsbCoxidised (summary available)

Summary:
DsbC is a periplasmic disulfide oxidoreductase which is thought to be the main catalyst of protein disulfide bond rearrangement in the periplasm although the protein also has disulfide oxidoreductase activity in vitro. DsbC, DsbD and thiordexin are the components of a pathway for protein disulfide bond isomerization in E. coli K-12 [Rietsch96]. Reducing potential is passed from cytoplasmic thioredoxin, through the DsbD membrane protein to periplasmic DsbC [Rietsch97].

dsbC null mutants show defects in formation of disulfide bond-containing proteins such as alkaline phosphatase and β-lactamase but do not affect the folding of OmpA [Missiakas94, Rietsch96]. Mouse urokinase (containing 12 disulfide bonds), expressed in E. coli does not fold properly in a dsbC null mutant [Rietsch96]. DsbC does not appear to be involved in disulfide bond formation in vivo [Rietsch96]. Purified DscbC reduces insulin in vitro [Missiakas94].

dsbC contains a CXXC motif that forms an unstable and reactive disulfide bond [Missiakas94, Zapun95]. Substitution of either of these cyteine residues results in loss of enzyme activity. Overexpression of dsbC can substitute for the loss of dsbA in vivo [Missiakas94]. DsbC forms a stable homodimeric complex. DsbC has a greater protein disulfide isomerizing activity than DsbA [Zapun95].

Dimeric DsbC is a V-shaped molecule with each monomer forming an arm of the 'V'. The N-terminal domain of each monomer forms the dimer interface at the base of the 'V'. The C-terminal domain contains the catalytic C98XXC101 motif. A second disulfide bond between Cys141 and Cys163 is also present in each monomer [McCarthy00].

DsbC has chaperone activity, promoting reactivation and suppressing aggregation of denatured D-glyceraldehyde-3-P dehydrogenase during refolding [Chen99a]. DsbC is part of a periplasmic reducing system that protects single cysteine residues in proteins from sulfanylation. Protein sulfenic acids accumulate in the periplasm of dsbC dsbG null strains [Depuydt09].

dsbC is one of a network of genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12].

Reviews: [Bardwell94, Inaba09]

Citations: [Arredondo09, Frishman96, Sone97, Joly97, Darby98, Maskos03, Segatori04, Shouldice10, Ito10]

Gene Citations: [Nonaka06, Rhodius05]

Locations: periplasmic space

Map Position: [3,036,134 <- 3,036,844] (65.44 centisomes)
Length: 711 bp / 236 aa

Molecular Weight of Polypeptide: 25.622 kD (from nucleotide sequence)

pI: 6.72

Isozyme Sequence Similarity:
protein disulfide oxidoreductase - DsbAreduced: NO

Unification Links: ASAP:ABE-0009494 , CGSC:33355 , DIP:DIP-35818N , EchoBASE:EB1063 , EcoGene:EG11070 , EcoliWiki:b2893 , IAF1260:2703933 , Mint:MINT-1288669 , ModBase:P0AEG6 , OU-Microarray:b2893 , PortEco:dsbC , PR:PRO_000022481 , Pride:P0AEG6 , Protein Model Portal:P0AEG6 , RegulonDB:EG11070 , SMR:P0AEG6 , String:511145.b2893 , Swiss-Model:P0AEG6 , UniProt:P0AEG6

Relationship Links: InterPro:IN-FAMILY:IPR009094 , InterPro:IN-FAMILY:IPR012336 , InterPro:IN-FAMILY:IPR017937 , InterPro:IN-FAMILY:IPR018950 , PDB:Structure:1EEJ , PDB:Structure:1G0T , PDB:Structure:1JZD , PDB:Structure:1JZO , PDB:Structure:1TJD , PDB:Structure:2IYJ , Pfam:IN-FAMILY:PF10411 , Pfam:IN-FAMILY:PF13098 , Prosite:IN-FAMILY:PS00194 , Prosite:IN-FAMILY:PS51352

In Paralogous Gene Group: 164 (2 members)

In Reactions of unknown directionality:

Not in pathways:
DsbDreduced[periplasmic space] + DsbCoxidized[periplasmic space] = DsbDoxidized[periplasmic space] + DsbCreduced[periplasmic space]

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006457 - protein folding Inferred from experiment [Missiakas94]
GO:0055114 - oxidation-reduction process Inferred from experiment [Depuydt09]
GO:0045454 - cell redox homeostasis Inferred by computational analysis [GOA01a]
Molecular Function: GO:0003756 - protein disulfide isomerase activity Inferred from experiment [Missiakas94]
GO:0015035 - protein disulfide oxidoreductase activity Inferred from experiment [Depuydt09]
GO:0042803 - protein homodimerization activity Inferred from experiment [McCarthy00, Zapun95]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Author statement Inferred from experiment Inferred by computational analysis [DiazMejia09, Han13, LopezCampistrou05, Missiakas94]
GO:0042597 - periplasmic space Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Missiakas94]

MultiFun Terms: information transfer protein related chaperoning, repair (refolding)

Essentiality data for dsbC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Last-Curated ? 27-Mar-2013 by Mackie A , Macquarie University


Enzymatic reaction of: protein disulfide isomerase

Synonyms: S-S rearrangase

EC Number: 5.3.4.1

a protein with incorrect disulfide bonds[periplasmic space] <=> a protein with correct disulfide bonds[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.


Enzymatic reaction of: protein disulfide oxidoreductase

Synonyms: thiol:disulfide interchange protein

a protein with reduced sulfide groups[periplasmic space] <=> a protein with oxidized disulfide bonds[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.


Sequence Features

Feature Class Location Citations Comment
Signal-Sequence 1 -> 20
[Link97, UniProt11]
.
Chain 21 -> 236
[UniProt09]
UniProt: Thiol:disulfide interchange protein dsbC;
Conserved-Region 36 -> 231
[UniProt09]
UniProt: Thioredoxin;
Mutagenesis-Variant 118
[Missiakas94, UniProt11]
Alternate sequence: C → A; UniProt: Loss of activity.
Alternate sequence: C → T; UniProt: Loss of activity.
Disulfide-Bond-Site 121, 118
[McCarthy00, UniProt11]
UniProt: Redox-active.
Mutagenesis-Variant 121
[Missiakas94, UniProt11]
Alternate sequence: C → V; UniProt: Loss of activity.
Alternate sequence: C → A; UniProt: Partial loss of activity.
Mutagenesis-Variant 161
[Missiakas94, UniProt11]
Alternate sequence: C → S; UniProt: Destabilization of protein.
Disulfide-Bond-Site 183, 161
[McCarthy00, UniProt11]
.
Mutagenesis-Variant 183
[Missiakas94, UniProt11]
Alternate sequence: C → L; UniProt: Destabilization of protein.
Sequence-Conflict 219
[Lovett91, UniProt10]
Alternate sequence: P → missing; UniProt: (in Ref. 1; AAA62788);


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b2893 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11070; confirmed by SwissProt match.


References

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Arredondo09: Arredondo SA, Chen TF, Riggs AF, Gilbert HF, Georgiou G (2009). "Role of dimerization in the catalytic properties of the Escherichia coli disulfide isomerase DsbC." J Biol Chem 284(36);23972-9. PMID: 19581640

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bardwell94: Bardwell JC (1994). "Building bridges: disulphide bond formation in the cell." Mol Microbiol 1994;14(2);199-205. PMID: 7830566

Chen99a: Chen J, Song JL, Zhang S, Wang Y, Cui DF, Wang CC (1999). "Chaperone activity of DsbC." J Biol Chem 1999;274(28);19601-5. PMID: 10391895

Darby98: Darby NJ, Raina S, Creighton TE (1998). "Contributions of substrate binding to the catalytic activity of DsbC." Biochemistry 37(3);783-91. PMID: 9454567

Depuydt09: Depuydt M, Leonard SE, Vertommen D, Denoncin K, Morsomme P, Wahni K, Messens J, Carroll KS, Collet JF (2009). "A periplasmic reducing system protects single cysteine residues from oxidation." Science 326(5956);1109-11. PMID: 19965429

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Frishman96: Frishman D (1996). "DSBC protein: a new member of the thioredoxin fold-containing family." Biochem Biophys Res Commun 1996;219(3);686-9. PMID: 8645242

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Han13: Han MJ, Kim JY, Kim JA (2013). "Comparison of the large-scale periplasmic proteomes of the Escherichia coli K-12 and B strains." J Biosci Bioeng. PMID: 24140104

Inaba09: Inaba K (2009). "Disulfide bond formation system in Eschericia coli." J Biochem 146(5):591-7. PMID: 19567379

Ito10: Ito K (2010). "Editing disulphide bonds: error correction using redox currencies." Mol Microbiol 75(1);1-5. PMID: 19906178

Joly97: Joly JC, Swartz JR (1997). "In vitro and in vivo redox states of the Escherichia coli periplasmic oxidoreductases DsbA and DsbC." Biochemistry 1997;36(33);10067-72. PMID: 9254601

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Lovett91: Lovett ST, Kolodner RD (1991). "Nucleotide sequence of the Escherichia coli recJ chromosomal region and construction of recJ-overexpression plasmids." J Bacteriol 173(1);353-64. PMID: 1987126

Maskos03: Maskos K, Huber-Wunderlich M, Glockshuber R (2003). "DsbA and DsbC-catalyzed oxidative folding of proteins with complex disulfide bridge patterns in vitro and in vivo." J Mol Biol 325(3);495-513. PMID: 12498799

McCarthy00: McCarthy AA, Haebel PW, Torronen A, Rybin V, Baker EN, Metcalf P (2000). "Crystal structure of the protein disulfide bond isomerase, DsbC, from Escherichia coli." Nat Struct Biol 7(3);196-9. PMID: 10700276

Missiakas94: Missiakas D, Georgopoulos C, Raina S (1994). "The Escherichia coli dsbC (xprA) gene encodes a periplasmic protein involved in disulfide bond formation." EMBO J 1994;13(8);2013-20. PMID: 8168498

Nonaka06: Nonaka G, Blankschien M, Herman C, Gross CA, Rhodius VA (2006). "Regulon and promoter analysis of the E. coli heat-shock factor, sigma32, reveals a multifaceted cellular response to heat stress." Genes Dev 20(13);1776-89. PMID: 16818608

Rhodius05: Rhodius VA, Suh WC, Nonaka G, West J, Gross CA (2005). "Conserved and variable functions of the sigmaE stress response in related genomes." PLoS Biol 4(1);e2. PMID: 16336047

Rietsch96: Rietsch A, Belin D, Martin N, Beckwith J (1996). "An in vivo pathway for disulfide bond isomerization in Escherichia coli." Proc Natl Acad Sci U S A 93(23);13048-53. PMID: 8917542

Rietsch97: Rietsch A, Bessette P, Georgiou G, Beckwith J (1997). "Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin." J Bacteriol 1997;179(21);6602-8. PMID: 9352906

Segatori04: Segatori L, Paukstelis PJ, Gilbert HF, Georgiou G (2004). "Engineered DsbC chimeras catalyze both protein oxidation and disulfide-bond isomerization in Escherichia coli: Reconciling two competing pathways." Proc Natl Acad Sci U S A 101(27);10018-23. PMID: 15220477

Shouldice10: Shouldice SR, Cho SH, Boyd D, Heras B, Eser M, Beckwith J, Riggs P, Martin JL, Berkmen M (2010). "In vivo oxidative protein folding can be facilitated by oxidation-reduction cycling." Mol Microbiol 75(1);13-28. PMID: 19968787

Sone97: Sone M, Akiyama Y, Ito K (1997). "Differential in vivo roles played by DsbA and DsbC in the formation of protein disulfide bonds." J Biol Chem 272(16);10349-52. PMID: 9099671

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Zapun95: Zapun A, Missiakas D, Raina S, Creighton TE (1995). "Structural and functional characterization of DsbC, a protein involved in disulfide bond formation in Escherichia coli." Biochemistry 1995;34(15);5075-89. PMID: 7536035

Other References Related to Gene Regulation

Dartigalongue01: Dartigalongue C, Missiakas D, Raina S (2001). "Characterization of the Escherichia coli sigma E regulon." J Biol Chem 276(24);20866-75. PMID: 11274153


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC14A.