Gene Symbol: ccmF
Description: heme lyase, CcmF subunit
Alias: ECK2188, JW2184, yejR
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. 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
    ..polypeptide accumulates in Escherichia coli K-12 mutants defective in an essential gene for cytochrome c assembly, ccmF, and speculated that this polypeptide is either CcmE or CcmG...
  2. 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. ..
  3. 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. ..
  4. San Francisco B, Bretsnyder E, Rodgers K, Kranz R. Heme ligand identification and redox properties of the cytochrome c synthetase, CcmF. Biochemistry. 2011;50:10974-85 pubmed publisher
    Cytochrome c maturation in many bacteria, archaea, and plant mitochondria involves the integral membrane protein CcmF, which is thought to function as a cytochrome c synthetase by facilitating the final covalent attachment of heme to the ..
  5. 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. ..
  6. 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
    ..bonds formed between correctly paired cysteine residues in the cytochrome c apoproteins prior to haem attachment by CcmF and CcmH...
  7. 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. ..
  8. 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. ..
  9. 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. ..

More Information


  1. 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...
  2. 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...
  3. 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...
  4. 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. ..
  5. 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. ..
  6. 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, ..
  7. 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
    ..However, the low level of holo-CcmE formed in the chimera is transferred efficiently to cytochrome c, indicating that heme delivery from CcmE does not involve the membrane anchor. ..
  8. 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
  9. 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. ..
  10. Turkarslan S, Sanders C, Daldal F. Extracytoplasmic prosthetic group ligation to apoproteins: maturation of c-type cytochromes. Mol Microbiol. 2006;60:537-41 pubmed
  11. 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. ..
  12. Lee J, Harvat E, Stevens J, Ferguson S, Saier M. Evolutionary origins of members of a superfamily of integral membrane cytochrome c biogenesis proteins. Biochim Biophys Acta. 2007;1768:2164-81 pubmed
    ..coli; cytochrome c biogenesis System I), CcmF (E...
  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
    ..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...
  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
    ..Genes similar to nrfE, nrfF and nrfG are present in the E. coli nap-ccm locus at minute 47. CcmF is similar to NrfE, the N-terminal region of CcmH is similar to NrfF and the C-terminal portion of CcmH is similar ..
  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. 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. ..
  17. 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
  18. 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. ..
  19. 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. ..
  20. 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
    ..Here, we report that CcmF is a key player in the late steps of cytochrome c maturation...
  21. 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. ..
  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. 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
  25. 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. ..
  26. 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. ..
  27. 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. ..
  28. 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. ..
  29. San Francisco B, Sutherland M, Kranz R. The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE. Mol Microbiol. 2014;91:996-1008 pubmed publisher
    ..Three conserved histidines in CcmF (TM-His1, TM-His2 and P-His1) are required for activity, as are the conserved cysteine pairs in CcmG and CcmH...
  30. 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
  31. 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 a periplasmic heme chaperone that binds heme covalently and transfers it onto apocytochrome c in the presence of CcmF, CcmG, and CcmH...
  32. 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. ..
  33. 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. ..
  34. 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. ..
  35. Meyer E, Giegé P, Gelhaye E, Rayapuram N, Ahuja U, Thöny Meyer L, et al. AtCCMH, an essential component of the c-type cytochrome maturation pathway in Arabidopsis mitochondria, interacts with apocytochrome c. Proc Natl Acad Sci U S A. 2005;102:16113-8 pubmed
    ..When expressed in Escherichia coli, AtCCMH coimmunoprecipitates with the bacterial CcmF, a proposed component of the heme lyase...
  36. 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...
  37. 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. ..
  38. 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. ..
  39. 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. ..
  40. 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. ..
  41. 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).
  42. 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
    ..The CcmABCDE proteins are proposed to traffic haem to the cytochrome c synthetase (CcmF/H) for covalent attachment to cytochrome c by unknown mechanisms...