Gene Symbol: ccmE
Description: periplasmic heme chaperone
Alias: ECK2189, JW2185, yejS
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Stevens J, Uchida T, Daltrop O, Ferguson S. Covalent cofactor attachment to proteins: cytochrome c biogenesis. Biochem Soc Trans. 2005;33:792-5 pubmed
    ..Unexpectedly, it has been found that the haem chaperone CcmE (cytochrome c maturation), which is an essential intermediate in the process, also binds haem covalently before ..
  2. Ahuja U, Thöny Meyer L. Dynamic features of a heme delivery system for cytochrome C maturation. J Biol Chem. 2003;278:52061-70 pubmed
    ..Heme is transferred to the periplasmic heme chaperone CcmE by CcmC and from there to apocytochrome c...
  3. 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
    b>CcmE is a heme chaperone involved in the periplasmic maturation of c-type cytochromes in many bacteria and plant mitochondria. It binds heme covalently and subsequently transfers it to the apo form of cytochromes c...
  4. 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
    ..COSY experiment to the 16 kDa apo-form of the E. coli Heme Chaperon protein CcmE is described...
  5. Feissner R, Richard Fogal C, Frawley E, Kranz R. ABC transporter-mediated release of a haem chaperone allows cytochrome c biogenesis. Mol Microbiol. 2006;61:219-31 pubmed
    ..involves an ATP-binding cassette (ABC) transporter that is required for release of the periplasmic haem chaperone CcmE to the last step of cytochrome c assembly...
  6. 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
  7. 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. ..
  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. 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
    ..A cis-proline located at the N-terminus of the first beta-strand of the betabetaalpha motif of the thioredoxin-like domain is a conserved structural feature of the thioredoxin superfamily. ..

More Information


  1. Schulz H, Pellicioli E, Thony Meyer L. New insights into the role of CcmC, CcmD and CcmE in the haem delivery pathway during cytochrome c maturation by a complete mutational analysis of the conserved tryptophan-rich motif of CcmC. Mol Microbiol. 2000;37:1379-88 pubmed
    ..b>CcmE is a mediator of haem delivery...
  2. 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. ..
  3. 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
    ..defective in an essential gene for cytochrome c assembly, ccmF, and speculated that this polypeptide is either CcmE or CcmG...
  4. 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
    ..but do not prove, the current view that CcmA, B, C and D are part of an essential haem transport mechanism, that CcmE, F and H are required for covalent haem attachment to cysteine-histidine motifs in cytochrome c apoproteins in the ..
  5. 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
    ..coli. This defect, but not that of the ccmG null mutant, could be complemented by adding low-molecular-weight thiol compounds to growing cells, which is in agreement with a reducing function for CcmG...
  6. 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. ..
  7. 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
    ..Additionally, while system I encodes a covalently bound haem chaperone (holo-CcmE), no covalent intermediate has been found in system II...
  8. 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
    ..Two unique structural features of CcmG-an acidic active site and an adjacent groove-appear to be necessary to convert an indiscriminately binding scaffold, the TRX fold, into a highly specific redox protein...
  9. 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
    ..cytochromes in many bacterial species and plant mitochondria requires the participation of the heme chaperone CcmE that binds heme covalently via a His residue (H130 in Escherichia coli) before transferring it stereospecifically ..
  10. Schulz H, Hennecke H, Thony Meyer L. Prototype of a heme chaperone essential for cytochrome c maturation. Science. 1998;281:1197-200 pubmed
    ..Here, an Escherichia coli hemoprotein, CcmE, was shown to bind heme in the bacterial periplasm by way of a single covalent bond to a histidine...
  11. 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
    ..The ccm mutants produce cytochrome c-550 polypeptide, but not holocytochrome c. Taken together the results demonstrate that heme can be transported to the periplasm by a ccm-independent mechanism...
  12. 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. ..
  13. 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
    ..The experiments are demonstrated with a 16 kDa (15)N, (13)C-labeled non-deuterated apo-CcmE and a 48 kDa uniformly (15)N, (13)C-labeled and fractionally ( approximately 90%) deuterated dimeric sFkpA...
  14. 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...
  15. 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. ..
  16. 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
    The cytochrome c maturation protein CcmE is an essential membrane-anchored heme chaperone involved in the post-translational covalent attachment of heme to c-type cytochromes in Gram-negative bacteria such as Escherichia coli...
  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. Thony Meyer L. Haem-polypeptide interactions during cytochrome c maturation. Biochim Biophys Acta. 2000;1459:316-24 pubmed
    ..At least three of them, CcmC, CcmE and CcmF, are thought to interact directly with haem...
  19. 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
    ..The data support a model proposed by others in which CcmG catalyses one of the last reactions specific to cytochrome c assembly. ..
  20. 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. ..
  21. 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
    b>CcmE is a heme chaperone that binds heme transiently in the periplasm of Escherichia coli and delivers it to newly synthesized and exported c-type cytochromes. The chemical nature of the covalent bond between heme and H130 is not known...
  22. 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
    ..Escherichia coli contains two monotopic membrane proteins with periplasmic, functional domains, the heme chaperone CcmE and the thioredoxin CcmG...
  23. 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. ..
  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
    ..The pathway includes (i) covalent, transient binding of heme to the periplasmic domain of the heme chaperone CcmE; (ii) the subsequent release of heme; and (iii) transfer and covalent attachment of heme to apocytochrome c...
  25. 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. ..
  26. 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
  27. 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
    ..b>CcmE is a periplasmic heme chaperone that binds heme covalently and transfers it onto apocytochrome c in the presence of ..
  28. Richard Fogal C, Kranz R. The CcmC:heme:CcmE complex in heme trafficking and cytochrome c biosynthesis. J Mol Biol. 2010;401:350-62 pubmed publisher
    ..g., apoCcmE for CcmC). Here, it is shown that CcmC is only trapped with heme when its cognate acceptor protein CcmE is present...
  29. 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
    ..This implies that the function of DsbE in cytochrome c maturation can be ascribed to its active-site cysteines and the structure of the reduced form...
  30. 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
    ..The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 35.48, b = 48.52, c = 84.78 A. X-ray data have been collected to 1.9 A resolution. ..
  31. 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. ..
  32. 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
  33. Ren Q, Thony Meyer L. Physical interaction of CcmC with heme and the heme chaperone CcmE during cytochrome c maturation. J Biol Chem. 2001;276:32591-6 pubmed
    ..In Escherichia coli, this process involves eight membrane proteins encoded by the ccmABCDEFGH operon. CcmE binds heme covalently and transfers it to apocytochromes c in the presence of other Ccm proteins...
  34. 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. ..
  35. 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
    ..This and other features, like the possibility of using an additional interaction surface, constitute the structural basis for the adaptability of nDsbD to different protein substrates. ..
  36. 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. ..
  37. Stevens J, Daltrop O, Higham C, Ferguson S. Interaction of heme with variants of the heme chaperone CcmE carrying active site mutations and a cleavable N-terminal His tag. J Biol Chem. 2003;278:20500-6 pubmed
    Cytochrome c maturation in the periplasms of many bacteria requires the heme chaperone CcmE, which binds heme covalently both in vivo and in vitro via a histidine residue before transferring the heme to apocytochromes c...
  38. Christensen O, Harvat E, Thöny Meyer L, Ferguson S, Stevens J. Loss of ATP hydrolysis activity by CcmAB results in loss of c-type cytochrome synthesis and incomplete processing of CcmE. FEBS J. 2007;274:2322-32 pubmed
    ..The same mutation does not prevent covalent attachment of heme to the heme chaperone CcmE, but holo-CcmE is, for some unidentified reason, incompetent for heme transfer to an apocytochrome c or for release ..
  39. 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).
  40. Allen J, Harvat E, Stevens J, Ferguson S. A variant System I for cytochrome c biogenesis in archaea and some bacteria has a novel CcmE and no CcmH. FEBS Lett. 2006;580:4827-34 pubmed
    ..relative to the well-studied apparatus from proteobacteria and plants is a novel form of the heme chaperone CcmE, lacking the highly conserved histidine that covalently binds heme and is essential for function in Escherichia ..
  41. García Rubio I, Braun M, Gromov I, Thöny Meyer L, Schweiger A. Axial coordination of heme in ferric CcmE chaperone characterized by EPR spectroscopy. Biophys J. 2007;92:1361-73 pubmed
    In Escherichia coli cytochrome c maturation requires a set of eight proteins including the heme chaperone CcmE, which binds heme transiently, yet covalently...
  42. 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. ..
  43. Skórko Glónekv J, Sobiecka A. [Periplasmatic disulfide oxidoreductases from bacterium Escherichia coli--their structure and function]. Postepy Biochem. 2005;51:459-67 pubmed
    ..The redox properties of Dsb proteins with the particular focus on structure-function dependence are in this review discussed. ..
  44. Daltrop O, Stevens J, Higham C, Ferguson S. The CcmE protein of the c-type cytochrome biogenesis system: unusual in vitro heme incorporation into apo-CcmE and transfer from holo-CcmE to apocytochrome. Proc Natl Acad Sci U S A. 2002;99:9703-8 pubmed
    Three key steps of cytochrome c biogenesis in many Gram-negative bacteria, the uptake of heme by the heme chaperone CcmE, the covalent attachment of heme to CcmE, and its subsequent release from CcmE to an apocytochrome c, have been ..
  45. 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
    ..We report the first structure of a heme chaperone, CcmE, which comprises these two functions...
  46. Enggist E, Thöny Meyer L. The C-terminal flexible domain of the heme chaperone CcmE is important but not essential for its function. J Bacteriol. 2003;185:3821-7 pubmed
    b>CcmE is a heme chaperone active in the cytochrome c maturation pathway of Escherichia coli. It first binds heme covalently to strictly conserved histidine H130 and subsequently delivers it to apo-cytochrome c...
  47. 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. Here, we investigate the basis for CcmG function and demonstrate the importance of acidic residues surrounding the redox-active center. ..
  48. Uchida T, Stevens J, Daltrop O, Harvat E, Hong L, Ferguson S, et al. The interaction of covalently bound heme with the cytochrome c maturation protein CcmE. J Biol Chem. 2004;279:51981-8 pubmed
    The heme chaperone CcmE is a novel protein that binds heme covalently via a histidine residue as part of its essential function in the process of cytochrome c biogenesis in many bacteria as well as plant mitochondria...
  49. Ahuja U, Thöny Meyer L. CcmD is involved in complex formation between CcmC and the heme chaperone CcmE during cytochrome c maturation. J Biol Chem. 2005;280:236-43 pubmed
    CcmD is a small membrane protein involved in heme delivery to the heme chaperone CcmE during cytochrome c maturation. Here we show that it physically interacts with CcmE and CcmC, another essential component of the heme delivery system...
  50. 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. ..
  51. 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. ..