Gene Symbol: dsbE
Description: periplasmic thioredoxin of cytochrome c-type biogenesis
Alias: ECK2187, JW2183, ccmG, yejQ
Species: Escherichia coli str. K-12 substr. MG1655
Products:     dsbE

Top Publications

  1. Ouyang N, Gao Y, Hu H, Xia Z. Crystal structures of E. coli CcmG and its mutants reveal key roles of the N-terminal beta-sheet and the fingerprint region. Proteins. 2006;65:1021-31 pubmed
    CcmG, also designated DsbE, functions as a periplasmic protein thiol:disulfide oxidoreductase and is required for cytochrome c maturation...
  2. Allen J, Barker P, Ferguson S. A cytochrome b562 variant with a c-type cytochrome CXXCH heme-binding motif as a probe of the Escherichia coli cytochrome c maturation system. J Biol Chem. 2003;278:52075-83 pubmed
    ..This contrasts with previous reports indicating that DsbA is essential for cytochrome c biogenesis in E. coli. ..
  3. Thony Meyer L. Biogenesis of respiratory cytochromes in bacteria. Microbiol Mol Biol Rev. 1997;61:337-76 pubmed
    ..Formation of the multisubunit cytochrome bc, complex and several terminal oxidases of the bo3, bd, aa3, and cbb3 types is discussed in detail, and models for linear maturation pathways are proposed wherever possible. ..
  4. Thony Meyer L. Haem-polypeptide interactions during cytochrome c maturation. Biochim Biophys Acta. 2000;1459:316-24 pubmed
    ..CcmC is required for binding of haem to CcmE, and CcmF for releasing it from CcmE and transferring it onto the apocytochrome. The mechanism by which haem crosses the cytoplasmic membrane is currently unknown. ..
  5. Schulz H, Fabianek R, Pellicioli E, Hennecke H, Thony Meyer L. Heme transfer to the heme chaperone CcmE during cytochrome c maturation requires the CcmC protein, which may function independently of the ABC-transporter CcmAB. Proc Natl Acad Sci U S A. 1999;96:6462-7 pubmed
    ..heme chaperone that binds heme covalently and transfers it onto apocytochrome c in the presence of CcmF, CcmG, and CcmH...
  6. Thony Meyer L, Fischer F, Kunzler P, Ritz D, Hennecke H. Escherichia coli genes required for cytochrome c maturation. J Bacteriol. 1995;177:4321-6 pubmed
    ..The results suggest that the E. coli ccm gene cluster present in the aeg-46.5 region is required for a general pathway involved in cytochrome c maturation. ..
  7. Richard Fogal C, Frawley E, Bonner E, Zhu H, San Francisco B, Kranz R. A conserved haem redox and trafficking pathway for cofactor attachment. EMBO J. 2009;28:2349-59 pubmed publisher
  8. Allen J, Sawyer E, Ginger M, Barker P, Ferguson S. Variant c-type cytochromes as probes of the substrate specificity of the E. coli cytochrome c maturation (Ccm) apparatus. Biochem J. 2009;419:177-84, 2 p following 184 pubmed publisher
    ..The implications of our observations for the haem-attachment reaction, for genome analyses and for the substrate specificity of the Ccm system, are discussed. ..
  9. Richard Fogal C, Frawley E, Feissner R, Kranz R. Heme concentration dependence and metalloporphyrin inhibition of the system I and II cytochrome c assembly pathways. J Bacteriol. 2007;189:455-63 pubmed
    ..We propose that the targets are the heme binding proteins in the pathways (CcmC, CcmE, and CcmF for system I and CcsA for system II). ..

More Information


  1. Stirnimann C, Rozhkova A, Grauschopf U, Grutter M, Glockshuber R, Capitani G. Structural basis and kinetics of DsbD-dependent cytochrome c maturation. Structure. 2005;13:985-93 pubmed
    ..coli transports two electrons from cytoplasmic thioredoxin to the periplasmic substrate proteins DsbC, DsbG and CcmG. DsbD consists of an N-terminal periplasmic domain (nDsbD), a C-terminal periplasmic domain, and a central ..
  2. Allen J, Leach N, Ferguson S. The histidine of the c-type cytochrome CXXCH haem-binding motif is essential for haem attachment by the Escherichia coli cytochrome c maturation (Ccm) apparatus. Biochem J. 2005;389:587-92 pubmed
  3. Stevens J, Gordon E, Ferguson S. Overproduction of CcmABCDEFGH restores cytochrome c maturation in a DsbD deletion strain of E. coli: another route for reductant?. FEBS Lett. 2004;576:81-5 pubmed
    ..The Ccm proteins do not, however, restore the normal disulfide mis-isomerisation phenotype of the deletion strain, as shown by assay of the multidisulfide-bonded enzyme urokinase. ..
  4. Fabianek R, Huber Wunderlich M, Glockshuber R, Kunzler P, Hennecke H, Thony Meyer L. Characterization of the Bradyrhizobium japonicum CycY protein, a membrane-anchored periplasmic thioredoxin that may play a role as a reductant in the biogenesis of c-type cytochromes. J Biol Chem. 1997;272:4467-73 pubmed
    ..This is in agreement with our hypothesis that CycY is required, directly or indirectly, for the reduction of the heme-binding site cysteines in the CXXCH motif of c-type apocytochromes before heme attachment occurs. ..
  5. Choe M, Reznikoff W. Anaerobically expressed Escherichia coli genes identified by operon fusion techniques. J Bacteriol. 1991;173:6139-46 pubmed
    ..5 expression were observed in all medium conditions regardless of the presence or absence of nitrate. This suggests that narL has a regulatory function in the absence of exogenously added nitrate. ..
  6. Harvat E, Redfield C, Stevens J, Ferguson S. Probing the heme-binding site of the cytochrome c maturation protein CcmE. Biochemistry. 2009;48:1820-8 pubmed publisher
    ..However, mutation of Y134 affected neither heme attachment to CcmE nor cytochrome c maturation, suggesting that heme binding and release from CcmE are hydrophobically driven and relatively indifferent to axial ligation. ..
  7. Reid E, Eaves D, Cole J. The CcmE protein from Escherichia coli is a haem-binding protein. FEMS Microbiol Lett. 1998;166:369-75 pubmed
    ..in an essential gene for cytochrome c assembly, ccmF, and speculated that this polypeptide is either CcmE or CcmG. The haem-containing polypeptide, which is associated with the cytoplasmic membrane, has now been identified by N-..
  8. Eaves D, Grove J, Staudenmann W, James P, Poole R, White S, et al. Involvement of products of the nrfEFG genes in the covalent attachment of haem c to a novel cysteine-lysine motif in the cytochrome c552 nitrite reductase from Escherichia coli. Mol Microbiol. 1998;28:205-16 pubmed
  9. Porat A, Cho S, Beckwith J. The unusual transmembrane electron transporter DsbD and its homologues: a bacterial family of disulfide reductases. Res Microbiol. 2004;155:617-22 pubmed
    ..Its substrates include protein disulfide isomerases and a protein involved in cytochrome c assembly. Two membrane-embedded cysteines in DsbD alternate between the disulfide-bonded (oxidized) and reduced states in this process. ..
  10. Hu K, Vögeli B, Pervushin K. Side-chain H and C resonance assignment in protonated/partially deuterated proteins using an improved 3D(13)C-detected HCC-TOCSY. J Magn Reson. 2005;174:200-8 pubmed
    ..It is predicted that this method should be suitable for the assignment of methyl (13)C and (1)H chemical shifts of methyl protonated, highly deuterated and (13)C-labeled proteins with even higher molecular weight. ..
  11. Feissner R, Richard Fogal C, Frawley E, Loughman J, Earley K, Kranz R. Recombinant cytochromes c biogenesis systems I and II and analysis of haem delivery pathways in Escherichia coli. Mol Microbiol. 2006;60:563-77 pubmed
    ..It is shown that this allows system I to use holo-CcmE as a haem reservoir, a capability system II does not possess. ..
  12. Edeling M, Guddat L, Fabianek R, Halliday J, Jones A, Thony Meyer L, et al. Crystallization and preliminary diffraction studies of native and selenomethionine CcmG (CycY, DsbE). Acta Crystallogr D Biol Crystallogr. 2001;57:1293-5 pubmed
    ..CcmG (DsbE) is a reducing Dsb protein required for cytochrome c maturation...
  13. Li Q, Hu H, Wang W, Xu G. Structural and redox properties of the leaderless DsbE (CcmG) protein: both active-site cysteines of the reduced form are involved in its function in the Escherichia coli periplasm. Biol Chem. 2001;382:1679-86 pubmed publisher
    ..play important roles in ensuring the correct formation of disulfide bonds, of which the DsbE protein, also called CcmG, is the one implicated in electron transfer for cytochrome c maturation in the periplasm of Escherichia coli...
  14. Grovc J, Busby S, Cole J. The role of the genes nrf EFG and ccmFH in cytochrome c biosynthesis in Escherichia coli. Mol Gen Genet. 1996;252:332-41 pubmed
    ..In contrast, NrfE and NrfG are proposed to fulfill a more specialised role in the assembly of the formate-dependent nitrite reductase. ..
  15. Grove J, Tanapongpipat S, Thomas G, Griffiths L, Crooke H, Cole J. Escherichia coli K-12 genes essential for the synthesis of c-type cytochromes and a third nitrate reductase located in the periplasm. Mol Microbiol. 1996;19:467-81 pubmed
    ..5' promoter) and from constitutive or weakly regulated promoters apparently located within the downstream nap and ccm genes. ..
  16. Messens J, Collet J. Pathways of disulfide bond formation in Escherichia coli. Int J Biochem Cell Biol. 2006;38:1050-62 pubmed
    ..This review focuses on the pathways of disulfide bond formation and isomerization in bacteria, taking Escherichia coli as a model. ..
  17. Turkarslan S, Sanders C, Daldal F. Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c-type cytochromes. Mol Microbiol. 2006;60:537-41 pubmed
  18. Fabianek R, Hofer T, Thony Meyer L. Characterization of the Escherichia coli CcmH protein reveals new insights into the redox pathway required for cytochrome c maturation. Arch Microbiol. 1999;171:92-100 pubmed
    ..We propose a model for the reaction sequence in which CcmH keeps the heme binding site of apocytochrome c in a reduced form for subsequent heme ligation. ..
  19. Enggist E, Thöny Meyer L, Güntert P, Pervushin K. NMR structure of the heme chaperone CcmE reveals a novel functional motif. Structure. 2002;10:1551-7 pubmed
    ..CcmE belongs to a family of proteins with a specific fold, which all share a function in delivery of specific molecular cargo. ..
  20. Stevens J, Uchida T, Daltrop O, Ferguson S. Covalent cofactor attachment to proteins: cytochrome c biogenesis. Biochem Soc Trans. 2005;33:792-5 pubmed
    ..Several in vitro and in vivo studies have provided insight into the function of this protein and into the overall process of cytochrome c biogenesis. ..
  21. Stevens J, Uchida T, Daltrop O, Kitagawa T, Ferguson S. Dynamic ligation properties of the Escherichia coli heme chaperone CcmE to non-covalently bound heme. J Biol Chem. 2006;281:6144-51 pubmed
  22. Allen J, Ferguson S. Variation of the axial haem ligands and haem-binding motif as a probe of the Escherichia coli c-type cytochrome maturation (Ccm) system. Biochem J. 2003;375:721-8 pubmed
  23. Harvat E, Stevens J, Redfield C, Ferguson S. Functional characterization of the C-terminal domain of the cytochrome c maturation protein CcmE. J Biol Chem. 2005;280:36747-53 pubmed
  24. Ren Q, Ahuja U, Thöny Meyer L. A bacterial cytochrome c heme lyase. CcmF forms a complex with the heme chaperone CcmE and CcmH but not with apocytochrome c. J Biol Chem. 2002;277:7657-63 pubmed
    ..We propose that CcmFH forms a bacterial heme lyase complex for the transfer of heme from CcmE to apocytochrome c. ..
  25. Choe M, Reznikoff W. Identification of the regulatory sequence of anaerobically expressed locus aeg-46.5. J Bacteriol. 1993;175:1165-72 pubmed
    ..The proposed NarL site was found in a perfect-symmetry element. The aeg-46.5 regulatory elements are adjacent to, but divergent from, those of the eco gene. ..
  26. Iobbi Nivol C, Crooke H, Griffiths L, Grove J, Hussain H, Pommier J, et al. A reassessment of the range of c-type cytochromes synthesized by Escherichia coli K-12. FEMS Microbiol Lett. 1994;119:89-94 pubmed
    ..No other c-type cytochrome was detected under any growth condition tested. ..
  27. Edeling M, Ahuja U, Heras B, Thöny Meyer L, Martin J. The acidic nature of the CcmG redox-active center is important for cytochrome c maturation in Escherichia coli. J Bacteriol. 2004;186:4030-3 pubmed
    ..One of these genes, ccmG, encodes a thioredoxin-like protein with unusually specific redox activity...
  28. Schulz H, Hennecke H, Thony Meyer L. Prototype of a heme chaperone essential for cytochrome c maturation. Science. 1998;281:1197-200 pubmed
    ..The heme was then released and delivered to apocytochrome c. Thus, CcmE can be viewed as a heme chaperone guiding heme to its appropriate biological partner and preventing illegitimate complex formation. ..
  29. Ouyang N, Chen W, Li Q, Gao Y, Hu H, Xia Z. Crystallization and preliminary crystallographic studies of Escherichia coli CcmG/DsbE protein. Acta Crystallogr D Biol Crystallogr. 2003;59:1674-5 pubmed
    b>CcmG/DsbE is a typical thiol/disulfide oxidoreductase, exhibiting a specific reducing activity in a highly oxidizing environment, and is involved in electron transfer during the maturation of c-type cytochromes...
  30. Vögeli B, Pervushin K. TROSY experiment for refinement of backbone psi and phi by simultaneous measurements of cross-correlated relaxation rates and 3,4J(H alpha HN) coupling constants. J Biomol NMR. 2002;24:291-300 pubmed
    ..coli Heme Chaperon protein CcmE is described. Overall good agreement is achieved between psi and phi angles measured with the new experiment and the average values determined from an ensemble of 20 NMR conformers. ..
  31. Fabianek R, Hennecke H, Thony Meyer L. Periplasmic protein thiol:disulfide oxidoreductases of Escherichia coli. FEMS Microbiol Rev. 2000;24:303-16 pubmed
    ..This review reflects the recently made efforts to elucidate the sources of oxidising and reducing power in the periplasm as well as the different properties of certain periplasmic protein thiol:disulfide oxidoreductases of E. coli. ..
  32. Tan J, Bardwell J. Key players involved in bacterial disulfide-bond formation. Chembiochem. 2004;5:1479-87 pubmed
  33. Edeling M, Guddat L, Fabianek R, Th ny Meyer L, Martin J. Structure of CcmG/DsbE at 1.14 A resolution: high-fidelity reducing activity in an indiscriminately oxidizing environment. Structure. 2002;10:973-9 pubmed
    b>CcmG is unlike other periplasmic thioredoxin (TRX)-like proteins in that it has a specific reducing activity in an oxidizing environment and a high fidelity of interaction...
  34. Reid E, Cole J, Eaves D. The Escherichia coli CcmG protein fulfils a specific role in cytochrome c assembly. Biochem J. 2001;355:51-8 pubmed
    ..A thioredoxin-like protein, CcmG, is one of 12 proteins required for their assembly in the periplasm...
  35. Fabianek R, Hennecke H, Th ny Meyer L. The active-site cysteines of the periplasmic thioredoxin-like protein CcmG of Escherichia coli are important but not essential for cytochrome c maturation in vivo. J Bacteriol. 1998;180:1947-50 pubmed
    A new member of the family of periplasmic protein thiol:disulfide oxidoreductases, CcmG (also called DsbE), was characterized with regard to its role in cytochrome c maturation in Escherichia coli...
  36. Darwin A, Stewart V. Nitrate and nitrite regulation of the Fnr-dependent aeg-46.5 promoter of Escherichia coli K-12 is mediated by competition between homologous response regulators (NarL and NarP) for a common DNA-binding site. J Mol Biol. 1995;251:15-29 pubmed
    ..5 binding site to regulate aeg-46.5 operon expression in response to nitrate and nitrite. Apparently, only the NarP protein is competent to activate transcription of the aeg-46.5 operon when bound to the -44.5 region...
  37. Kranz R, Lill R, Goldman B, Bonnard G, Merchant S. Molecular mechanisms of cytochrome c biogenesis: three distinct systems. Mol Microbiol. 1998;29:383-96 pubmed
    ..The third system has evolved specifically in mitochondria of fungi, invertebrates and vertebrates. For system III, a pivotal role is played by an enzyme called cytochrome c haem lyase (CCHL) in the mitochondrial intermembrane space. ..
  38. Throne Holst M, Thony Meyer L, Hederstedt L. Escherichia coli ccm in-frame deletion mutants can produce periplasmic cytochrome b but not cytochrome c. FEBS Lett. 1997;410:351-5 pubmed
    ..coli ccmA and ccmC in-frame deletion mutants. Mutants deleted for ccmF or ccmG encoding a component of a putative cytochrome c-heme lyase and a membrane bound thioredoxin-like protein, ..
  39. Ortenberg R, Beckwith J. Functions of thiol-disulfide oxidoreductases in E. coli: redox myths, realities, and practicalities. Antioxid Redox Signal. 2003;5:403-11 pubmed
  40. Ahuja U, Thöny Meyer L. The membrane anchors of the heme chaperone CcmE and the periplasmic thioredoxin CcmG are functionally important. FEBS Lett. 2006;580:216-22 pubmed
    ..two monotopic membrane proteins with periplasmic, functional domains, the heme chaperone CcmE and the thioredoxin CcmG. We show in a domain swap experiment that the membrane anchors of these proteins can be exchanged without drastic ..
  41. Tanapongpipat S, Reid E, Cole J, Crooke H. Transcriptional control and essential roles of the Escherichia coli ccm gene products in formate-dependent nitrite reduction and cytochrome c synthesis. Biochem J. 1998;334 ( Pt 2):355-65 pubmed
    ..H are required for covalent haem attachment to cysteine-histidine motifs in cytochrome c apoproteins in the periplasm, and that CcmG is required for the reduction of cysteine residues on apocytochromes c in preparation for haem ligation.
  42. Enggist E, Schneider M, Schulz H, Thöny Meyer L. Biochemical and mutational characterization of the heme chaperone CcmE reveals a heme binding site. J Bacteriol. 2003;185:175-83 pubmed
    ..Isolation and characterization of the heme-binding peptides obtained after a tryptic digest of wild-type and H130C CcmE support the hypothesis that heme is bound covalently at a vinyl group. ..
  43. Skórko Glónekv J, Sobiecka A. [Periplasmatic disulfide oxidoreductases from bacterium Escherichia coli--their structure and function]. Postepy Biochem. 2005;51:459-67 pubmed
    ..1) oxidizing (DsbA/DsbB system), responsible for introducing S-S bonds, and (2) reducing (DsbC/DsbD system, DsbG, CcmG and CcmH) which acts to isomerase wrongly formed disulfide bonds and participates in maturation of cytochrome c...