Cellular and Molecular Life Sciences

, Volume 71, Issue 2, pp 229–255 | Cite as

The role of key residues in structure, function, and stability of cytochrome-c

  • Sobia Zaidi
  • Md. Imtaiyaz Hassan
  • Asimul Islam
  • Faizan Ahmad
Review

Abstract

Cytochrome-c (cyt-c), a multi-functional protein, plays a significant role in the electron transport chain, and thus is indispensable in the energy-production process. Besides being an important component in apoptosis, it detoxifies reactive oxygen species. Two hundred and eighty-five complete amino acid sequences of cyt-c from different species are known. Sequence analysis suggests that the number of amino acid residues in most mitochondrial cyts-c is in the range 104 ± 10, and amino acid residues at only few positions are highly conserved throughout evolution. These highly conserved residues are Cys14, Cys17, His18, Gly29, Pro30, Gly41, Asn52, Trp59, Tyr67, Leu68, Pro71, Pro76, Thr78, Met80, and Phe82. These are also known as “key residues”, which contribute significantly to the structure, function, folding, and stability of cyt-c. The three-dimensional structure of cyt-c from ten eukaryotic species have been determined using X-ray diffraction studies. Structure analysis suggests that the tertiary structure of cyt-c is almost preserved along the evolutionary scale. Furthermore, residues of N/C-terminal helices Gly6, Phe10, Leu94, and Tyr97 interact with each other in a specific manner, forming an evolutionary conserved interface. To understand the role of evolutionary conserved residues on structure, stability, and function, numerous studies have been performed in which these residues were substituted with different amino acids. In these studies, structure deals with the effect of mutation on secondary and tertiary structure measured by spectroscopic techniques; stability deals with the effect of mutation on Tm (midpoint of heat denaturation), ∆GD (Gibbs free energy change on denaturation) and folding; and function deals with the effect of mutation on electron transport, apoptosis, cell growth, and protein expression. In this review, we have compiled all these studies at one place. This compilation will be useful to biochemists and biophysicists interested in understanding the importance of conservation of certain residues throughout the evolution in preserving the structure, function, and stability in proteins.

Keywords

Cytochrome-c Key residues Folding and stability Natural selection Electron transport chain Apoptosis 

Supplementary material

18_2013_1341_MOESM1_ESM.pdf (772 kb)
Supplementary material 1 (PDF 771 kb)
18_2013_1341_MOESM2_ESM.pdf (60 kb)
Supplementary material 2 (PDF 60 kb)
18_2013_1341_MOESM3_ESM.docx (34 kb)
Supplementary material 3 (DOCX 34 kb)
18_2013_1341_MOESM4_ESM.doc (3.3 mb)
Supplementary material 4 (DOC 3387 kb)

References

  1. 1.
    Pettigrew GW, Moore GR (1987) Cytochrome c: biological aspects. Springer, Berlin Heidelberg New YorkGoogle Scholar
  2. 2.
    Moore GR, Pettigrew GW (1990) Cytochromes c: evolutionary, structural and physicochemical aspects. Springer, Berlin Heidelberg New York, pp 831–833Google Scholar
  3. 3.
    Kalanxhi E, Wallace CJ (2007) Cytochrome c impaled: investigation of the extended lipid anchorage of a soluble protein to mitochondrial membrane models. Biochem J 407:179–187PubMedGoogle Scholar
  4. 4.
    Orrenius S (2004) Mitochondrial regulation of apoptotic cell death. Toxicol Lett 149:19–23PubMedGoogle Scholar
  5. 5.
    Abdullaev Z, Bodrova ME, Chernyak BV et al (2002) A cytochrome c mutant with high electron transfer and antioxidant activities but devoid of apoptogenic effect. Biochem J 362:749–754PubMedGoogle Scholar
  6. 6.
    Pereverzev MO, Vygodina TV, Konstantinov AA, Skulachev VP (2003) Cytochrome c, an ideal antioxidant. Biochem Soc Trans 31:1312–1315PubMedGoogle Scholar
  7. 7.
    Skulachev VP (1998) Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 423:275–280PubMedGoogle Scholar
  8. 8.
    Belikova NA, Vladimirov YA, Osipov AN et al (2006) Peroxidase activity and structural transitions of cytochrome c bound to cardiolipin-containing membranes. Biochemistry 45:4998–5009PubMedCentralPubMedGoogle Scholar
  9. 9.
    Garcia-Heredia JM, Diaz-Moreno I, Nieto PM et al (2010) Nitration of tyrosine 74 prevents human cytochrome c to play a key role in apoptosis signaling by blocking caspase-9 activation. Biochim Biophys Acta 1797:981–993PubMedGoogle Scholar
  10. 10.
    Kapralov AA, Kurnikov IV, Vlasova II et al (2007) The hierarchy of structural transitions induced in cytochrome c by anionic phospholipids determines its peroxidase activation and selective peroxidation during apoptosis in cells. Biochemistry 46:14232–14244PubMedGoogle Scholar
  11. 11.
    Kapralov AA, Yanamala N, Tyurina YY et al (2011) Topography of tyrosine residues and their involvement in peroxidation of polyunsaturated cardiolipin in cytochrome c/cardiolipin peroxidase complexes. Biochim Biophys Acta 1808:2147–2155PubMedCentralPubMedGoogle Scholar
  12. 12.
    Pecina P, Borisenko GG, Belikova NA et al (2010) Phosphomimetic substitution of cytochrome C tyrosine 48 decreases respiration and binding to cardiolipin and abolishes ability to trigger downstream caspase activation. Biochemistry 49:6705–6714PubMedGoogle Scholar
  13. 13.
    Ying T, Wang ZH, Lin YW et al (2009) Tyrosine-67 in cytochrome c is a possible apoptotic trigger controlled by hydrogen bonds via a conformational transition. Chem Commun (Camb) 30:4512–4514Google Scholar
  14. 14.
    Liu Z, Lin H, Ye S et al (2006) Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis. Proc Natl Acad Sci USA 103:8965–8970PubMedGoogle Scholar
  15. 15.
    Koonin EV, Aravind L (2002) Origin and evolution of eukaryotic apoptosis: the bacterial connection. Cell Death Differ 9:394–404PubMedGoogle Scholar
  16. 16.
    Tezcan FA, Findley WM, Crane BR et al (2002) Using deeply trapped intermediates to map the cytochrome c folding landscape. Proc Natl Acad Sci USA 99:8626–8630PubMedGoogle Scholar
  17. 17.
    Yeh SR, Rousseau DL (1998) Folding intermediates in cytochrome c. Nat Struct Biol 5:222–228PubMedGoogle Scholar
  18. 18.
    Cianetti S, Negrerie M, Vos MH et al (2004) Photodissociation of heme distal methionine in ferrous cytochrome C revealed by subpicosecond time-resolved resonance Raman spectroscopy. J Am Chem Soc 126:13932–13933PubMedGoogle Scholar
  19. 19.
    Banci L, Bertini I, Rosato A, Varani G (1999) Mitochondrial cytochromes c: a comparative analysis. J Biol Inorg Chem 4:824–837PubMedGoogle Scholar
  20. 20.
    Dickerson RE (1971) Sequence and structure homologies in bacterial and mammalian-type cytochromes. J Mol Biol 57:1–15PubMedGoogle Scholar
  21. 21.
    Ferguson-Miller S, Brautigan DL, Margoliash E (1976) Correlation of the kinetics of electron transfer activity of various eukaryotic cytochromes c with binding to mitochondrial cytochrome c oxidase. J Biol Chem 251:1104–1115PubMedGoogle Scholar
  22. 22.
    Filosa A, English AM (2000) Probing local thermal stabilities of bovine, horse, and tuna ferricytochromes c at pH 7. J Biol Inorg Chem 5:448–454PubMedGoogle Scholar
  23. 23.
    Fredericks ZL, Pielak GJ (1993) Exploring the interface between the N- and C-terminal helices of cytochrome c by random mutagenesis within the C-terminal helix. Biochemistry 32:929–936PubMedGoogle Scholar
  24. 24.
    Knapp JA, Pace CN (1974) Guanidine hydrochloride and acid denaturation of horse, cow, and Candida krusei cytochromes c. Biochemistry 13:1289–1294PubMedGoogle Scholar
  25. 25.
    McLendon G, Smith M (1978) Equilibrium and kinetic studies of unfolding of homologous cytochromes c. J Biol Chem 253:4004–4008PubMedGoogle Scholar
  26. 26.
    Yuan X, Hawkridge FM, Chlebowski JF (1993) Thermodynamic and kinetic studies of cytochrome c from different species. J Electroanal Chem 350:29–42Google Scholar
  27. 27.
    Moza B, Qureshi SH, Ahmad F (2003) Equilibrium studies of the effect of difference in sequence homology on the mechanism of denaturation of bovine and horse cytochromes-c. Biochim Biophys Acta 1646:49–56PubMedGoogle Scholar
  28. 28.
    Hampsey DM, Das G, Sherman F (1986) Amino acid replacements in yeast iso-1-cytochrome c. Comparison with the phylogenetic series and the tertiary structure of related cytochromes c. J Biol Chem 261:3259–3271PubMedGoogle Scholar
  29. 29.
    Smith M (1986) Site-directed mutagenesis. Phil Trans R SOC Lond A 317:295–304Google Scholar
  30. 30.
    Zoller MJ, Smith M (1983) Oligonucleotide-directed mutagenesis of DNA fragments cloned into M13 vectors. Methods Enzymol 100:468–500PubMedGoogle Scholar
  31. 31.
    Sherman F, Stewart JW (1974) Variation of mutagenic action on nonsense mutants at different sites in the iso-1-cytochrome c gene of yeast. Genetics 78:97–113PubMedGoogle Scholar
  32. 32.
    Sherman F, Stewart JW, Parker JH et al (1968) The mutational alteration of the primary structure of yeast iso-1-cytochrome c. J Biol Chem 243:5446–5456PubMedGoogle Scholar
  33. 33.
    Brown GC, Borutaite V (2008) Regulation of apoptosis by the redox state of cytochrome c. Biochim Biophys Acta 1777:877–881PubMedGoogle Scholar
  34. 34.
    Jemmerson R, Liu J, Hausauer D et al (1999) A conformational change in cytochrome c of apoptotic and necrotic cells is detected by monoclonal antibody binding and mimicked by association of the native antigen with synthetic phospholipid vesicles. Biochemistry 38:3599–3609PubMedGoogle Scholar
  35. 35.
    Ow YP, Green DR, Hao Z, Mak TW (2008) Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol 9:532–542PubMedGoogle Scholar
  36. 36.
    Huttemann M, Pecina P, Rainbolt M et al (2011) The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis. Mitochondrion 11:369–381PubMedCentralPubMedGoogle Scholar
  37. 37.
    Rumbley JN, Hoang L, Englander SW (2002) Recombinant equine cytochrome c in Escherichia coli: high-level expression, characterization, and folding and assembly mutants. Biochemistry 41:13894–13901PubMedGoogle Scholar
  38. 38.
    Russell BS, Melenkivitz R, Bren KL (2000) NMR investigation of ferricytochrome c unfolding: detection of an equilibrium unfolding intermediate and residual structure in the denatured state. Proc Natl Acad Sci USA 97:8312–8317PubMedGoogle Scholar
  39. 39.
    Sambongi Y, Uchiyama S, Kobayashi Y et al (2002) Cytochrome c from a thermophilic bacterium has provided insights into the mechanisms of protein maturation, folding, and stability. Eur J Biochem 269:3355–3361PubMedGoogle Scholar
  40. 40.
    Santucci R, Bongiovanni C, Mei G et al (2000) Anion size modulates the structure of the A state of cytochrome c. Biochemistry 39:12632–12638PubMedGoogle Scholar
  41. 41.
    Sauder JM, Roder H (1998) Amide protection in an early folding intermediate of cytochrome c. Fold Des 3:293–301PubMedGoogle Scholar
  42. 42.
    Schweitzer-Stenner R, Shah R, Hagarman A, Dragomir I (2007) Conformational substates of horse heart cytochrome c exhibit different thermal unfolding of the heme cavity. J Phys Chem B 111:9603–9607PubMedGoogle Scholar
  43. 43.
    Smith LJ, Kahraman A, Thornton JM (2010) Heme proteins–diversity in structural characteristics, function, and folding. Proteins 78:2349–2368PubMedGoogle Scholar
  44. 44.
    Telford JR, Tezcan FA, Gray HB, Winkler JR (1999) Role of ligand substitution in ferrocytochrome c folding. Biochemistry 38:1944–1949PubMedGoogle Scholar
  45. 45.
    Thomas YG, Goldbeck RA, Kliger DS (2000) Characterization of equilibrium intermediates in denaturant-induced unfolding of ferrous and ferric cytochromes c using magnetic circular dichroism, circular dichroism, and optical absorption spectroscopies. Biopolymers 57:29–36PubMedGoogle Scholar
  46. 46.
    Zhong S, Rousseau DL, Yeh SR (2004) Modulation of the folding energy landscape of cytochrome c with salt. J Am Chem Soc 126:13934–13935PubMedGoogle Scholar
  47. 47.
    Goldbeck RA, Chen E, Kliger DS (2009) Early events, kinetic intermediates and the mechanism of protein folding in cytochrome c. Int J Mol Sci 10:1476–1499PubMedCentralPubMedGoogle Scholar
  48. 48.
    Levinthal C (1968) Are there pathways for protein folding? J Chim Phys 65:44–45Google Scholar
  49. 49.
    Dill KA, Phillips AT, Rosen JB (1997) Protein structure and energy landscape dependence on sequence using a continuous energy function. J Comput Biol 4:227–239PubMedGoogle Scholar
  50. 50.
    Dill KA, Chan HS (1997) From Levinthal to pathways to funnels. Nat Struct Biol 4:10–19PubMedGoogle Scholar
  51. 51.
    Dill KA, Ozkan SB, Weikl TR et al (2007) The protein folding problem: when will it be solved? Curr Opin Struct Biol 17:342–346PubMedGoogle Scholar
  52. 52.
    Dill KA, Ozkan SB, Shell MS, Weikl TR (2008) The protein folding problem. Annu Rev Biophys 37:289–316PubMedCentralPubMedGoogle Scholar
  53. 53.
    Jha SK, Udgaonkar JB (2010) Free energy barriers in protein folding and unfolding reactions. Curr Sci 99:457–475Google Scholar
  54. 54.
    Sinha KK, Udgaonkar JB (2009) Early events in protein folding. Curr Sci 96:1053–1070Google Scholar
  55. 55.
    Bolen DW, Rose GD (2008) Structure and energetics of the hydrogen-bonded backbone in protein folding. Annu Rev Biochem 77:339–362PubMedGoogle Scholar
  56. 56.
    Daggett V, Fersht AR (2003) Is there a unifying mechanism for protein folding? Trends Biochem Sci 28:18–25PubMedGoogle Scholar
  57. 57.
    Vertrees J, Wrabl JO, Hilser VJ (2009) Energetic profiling of protein folds. Methods Enzymol 455:299–327PubMedGoogle Scholar
  58. 58.
    Arai M, Kuwajima K (2000) Role of the molten globule state in protein folding. Adv Protein Chem 53:209–282PubMedGoogle Scholar
  59. 59.
    Ptitsyn OB (1995) Structures of folding intermediates. Curr Opin Struct Biol 5:74–78PubMedGoogle Scholar
  60. 60.
    Ptitsyn OB (1995) How the molten globule became. Trends Biochem Sci 20:376–379PubMedGoogle Scholar
  61. 61.
    Udgaonkar JB (2008) Multiple routes and structural heterogeneity in protein folding. Annu Rev Biophys 37:489–510PubMedGoogle Scholar
  62. 62.
    Yamada S, Bouley Ford ND, Keller GE et al (2013) Snapshots of a protein folding intermediate. Proc Natl Acad Sci USA 110:1606–1610PubMedGoogle Scholar
  63. 63.
    Travaglini-Allocatelli C, Gianni S, Brunori M (2004) A common folding mechanism in the cytochrome c family. Trends Biochem Sci 29:535–541PubMedGoogle Scholar
  64. 64.
    Thielges MC, Zimmermann J, Dawson PE, Romesberg FE (2009) The determinants of stability and folding in evolutionarily diverged cytochromes c. J Mol Biol 388:159–167PubMedCentralPubMedGoogle Scholar
  65. 65.
    Qureshi SH, Moza B, Yadav S, Ahmad F (2003) Conformational and thermodynamic characterization of the molten globule state occurring during unfolding of cytochromes-c by weak salt denaturants. Biochemistry 42:1684–1695PubMedGoogle Scholar
  66. 66.
    Ahmad Z, Ahmad F (1994) Physico-chemical characterization of products of unfolding of cytochrome c by calcium chloride. Biochim Biophys Acta 1207:223–230PubMedGoogle Scholar
  67. 67.
    Alam Khan MK, Rahaman MH, Hassan MI et al (2010) Conformational and thermodynamic characterization of the premolten globule state occurring during unfolding of the molten globule state of cytochrome c. J Biol Inorg Chem 15:1319–1329PubMedGoogle Scholar
  68. 68.
    Bai Y (1999) Kinetic evidence for an on-pathway intermediate in the folding of cytochrome c. Proc Natl Acad Sci USA 96:477–480PubMedGoogle Scholar
  69. 69.
    Bhuyan AK, Udgaonkar JB (2001) Folding of horse cytochrome c in the reduced state. J Mol Biol 312:1135–1160PubMedGoogle Scholar
  70. 70.
    Bhuyan AK, Rao DK, Prabhu NP (2005) Protein folding in classical perspective: folding of horse cytochrome c. Biochemistry 44:3034–3040PubMedGoogle Scholar
  71. 71.
    Colon W, Roder H (1996) Kinetic intermediates in the formation of the cytochrome c molten globule. Nat Struct Biol 3:1019–1025PubMedGoogle Scholar
  72. 72.
    Englander SW (2000) Protein folding intermediates and pathways studied by hydrogen exchange. Annu Rev Biophys Biomol Struct 29:213–238PubMedGoogle Scholar
  73. 73.
    Goto Y, Hagihara Y, Hamada D et al (1993) Acid-induced unfolding and refolding transitions of cytochrome c: a three-state mechanism in H2O and D2O. Biochemistry 32:11878–11885PubMedGoogle Scholar
  74. 74.
    Hamada D, Hoshino M, Kataoka M et al (1993) Intermediate conformational states of apocytochrome c. Biochemistry 32:10351–10358PubMedGoogle Scholar
  75. 75.
    Prabhu NP, Kumar R, Bhuyan AK (2004) Folding barrier in horse cytochrome c: support for a classical folding pathway. J Mol Biol 337:195–208PubMedGoogle Scholar
  76. 76.
    Moza B, Qureshi SH, Islam A et al (2006) A unique molten globule state occurs during unfolding of cytochrome c by LiClO4 near physiological pH and temperature: structural and thermodynamic characterization. Biochemistry 45:4695–4702PubMedGoogle Scholar
  77. 77.
    Lyubovitsky JG, Gray HB, Winkler JR (2002) Mapping the cytochrome C folding landscape. J Am Chem Soc 124:5481–5485PubMedGoogle Scholar
  78. 78.
    Pletneva EV, Gray HB, Winkler JR (2005) Many faces of the unfolded state: conformational heterogeneity in denatured yeast cytochrome C. J Mol Biol 345:855–867PubMedGoogle Scholar
  79. 79.
    Pletneva EV, Gray HB, Winkler JR (2005) Snapshots of cytochrome c folding. Proc Natl Acad Sci USA 102:18397–18402PubMedGoogle Scholar
  80. 80.
    Pletneva EV, Zhao Z, Kimura T et al (2007) Probing the cytochrome c’ folding landscape. J Inorg Biochem 101:1768–1775PubMedCentralPubMedGoogle Scholar
  81. 81.
    Bandi S, Bowler BE (2008) Probing the bottom of a folding funnel using conformationally gated electron transfer reactions. J Am Chem Soc 130:7540–7541PubMedGoogle Scholar
  82. 82.
    Hammack B, Godbole S, Bowler BE (1998) Cytochrome c folding traps are not due solely to histidine-heme ligation: direct demonstration of a role for N-terminal amino group-heme ligation. J Mol Biol 275:719–724PubMedGoogle Scholar
  83. 83.
    Marmorino JL, Lehti M, Pielak GJ (1998) Native tertiary structure in an A-state. J Mol Biol 275:379–388PubMedGoogle Scholar
  84. 84.
    Gianni S, Travaglini-Allocatelli C, Cutruzzola F et al (2001) Snapshots of protein folding. A study on the multiple transition state pathway of cytochrome c(551) from Pseudomonas aeruginosa. J Mol Biol 309:1177–1187PubMedGoogle Scholar
  85. 85.
    Gianni S, Travaglini-Allocatelli C, Cutruzzola F et al (2003) Parallel pathways in cytochrome c(551) folding. J Mol Biol 330:1145–1152PubMedGoogle Scholar
  86. 86.
    Travaglini-Allocatelli C, Cutruzzola F, Bigotti MG et al (1999) Folding mechanism of Pseudomonas aeruginosa cytochrome c551: role of electrostatic interactions on the hydrophobic collapse and transition state properties. J Mol Biol 289:1459–1467PubMedGoogle Scholar
  87. 87.
    Travaglini-Allocatelli C, Gianni S, Morea V et al (2003) Exploring the cytochrome c folding mechanism: cytochrome c552 from thermus thermophilus folds through an on-pathway intermediate. J Biol Chem 278:41136–41140PubMedGoogle Scholar
  88. 88.
    Alam Khan MK, Das U, Rahaman MH et al (2009) A single mutation induces molten globule formation and a drastic destabilization of wild-type cytochrome c at pH 6.0. J Biol Inorg Chem 14:751–760PubMedGoogle Scholar
  89. 89.
    Bertini I, Turano P, Vasos PR et al (2004) Cytochrome c and SDS: a molten globule protein with altered axial ligation. J Mol Biol 336:489–496PubMedGoogle Scholar
  90. 90.
    Nakamura S, Seki Y, Katoh E, Kidokoro S (2011) Thermodynamic and structural properties of the acid molten globule state of horse cytochrome C. Biochemistry 50:3116–3126PubMedGoogle Scholar
  91. 91.
    Wittung-Stafshede P (1998) A stable, molten-globule-like cytochrome c. Biochim Biophys Acta 1382:324–332PubMedGoogle Scholar
  92. 92.
    Khan MK, Rahaman H, Ahmad F (2011) Conformation and thermodynamic stability of pre-molten and molten globule states of mammalian cytochromes-c. Metallomics 3:327–338PubMedGoogle Scholar
  93. 93.
    Alber T (1989) Mutational effects on protein stability. Annu Rev Biochem 58:765–798PubMedGoogle Scholar
  94. 94.
    Santucci R, Ascoli F (1997) The Soret circular dichroism spectrum as a probe for the heme Fe(III)-Met(80) axial bond in horse cytochrome c. J Inorg Biochem 68:211–214PubMedGoogle Scholar
  95. 95.
    Schejter A, Plotkin B, Vig I (1991) The reactivity of cytochrome c with soft ligands. FEBS Lett 280:199–201PubMedGoogle Scholar
  96. 96.
    Davis LA, Schejter A, Hess GP (1974) Alkaline isomerization of oxidized cytochrome c. Equilibrium and kinetic measurements. J Biol Chem 249:2624–2632PubMedGoogle Scholar
  97. 97.
    Ferrer JC, Guillemette JG, Bogumil R et al (1993) Identification of Lys79 as an iron ligand in one form of alkaline yeast iso-1-ferricytochrome c. J Am Chem Soc 90:7507Google Scholar
  98. 98.
    Feinberg BA, Petro L, Hock G et al (1999) Using entropies of reaction to predict changes in protein stability: tyrosine-67-phenylalanine variants of rat cytochrome c and yeast Iso-1 cytochromes c. J Pharm Biomed Anal 19:115–125PubMedGoogle Scholar
  99. 99.
    Battistuzzi G, Borsari M, Cowan JA et al (2002) Control of cytochrome C redox potential: axial ligation and protein environment effects. J Am Chem Soc 124:5315–5324PubMedGoogle Scholar
  100. 100.
    Kassner RJ (1973) A theoretical model for the effects of local nonpolar heme environments on the redox potentials in cytochromes. J Am Chem Soc 95:2674–2677PubMedGoogle Scholar
  101. 101.
    Stellwagen E (1978) Haem exposure as the determinate of oxidation-reduction potential of haem proteins. Nature 275:73–74PubMedGoogle Scholar
  102. 102.
    Bertrand P, Mbarki O, Asso M et al (1995) Control of the redox potential in c-type cytochromes: importance of the entropic contribution. Biochemistry 34:11071–11079PubMedGoogle Scholar
  103. 103.
    Churg AK, Warshel A (1986) Control of the redox potential of cytochrome c and microscopic dielectric effects in proteins. Biochemistry 25:1675–1681PubMedGoogle Scholar
  104. 104.
    Rees DC (1985) Electrostatic influence on energetics of electron transfer reactions. Proc Natl Acad Sci USA 82:3082–3085PubMedGoogle Scholar
  105. 105.
    Tai H, Mikami S, Irie K et al (2010) Role of a highly conserved electrostatic interaction on the surface of cytochrome C in control of the redox function. Biochemistry 49:42–48PubMedGoogle Scholar
  106. 106.
    Wells JA (1990) Additivity of mutational effects in proteins. Biochemistry 29:8509–8517PubMedGoogle Scholar
  107. 107.
    Hoang L, Maity H, Krishna MM et al (2003) Folding units govern the cytochrome c alkaline transition. J Mol Biol 331:37–43PubMedGoogle Scholar
  108. 108.
    Lett CM, Rosu-Myles MD, Frey HE, Guillemette JG (1999) Rational design of a more stable yeast iso-1-cytochrome c. Biochim Biophys Acta 1432:40–48PubMedGoogle Scholar
  109. 109.
    Sanishvili R, Volz KW, Westbrook EM, Margoliash E (1995) The low ionic strength crystal structure of horse cytochrome c at 2.1 Å resolution and comparison with its high ionic strength counterpart. Structure 3:707–716PubMedGoogle Scholar
  110. 110.
    Mirkin N, Jaconcic J, Stojanoff V, Moreno A (2008) High resolution X-ray crystallographic structure of bovine heart cytochrome c and its application to the design of an electron transfer biosensor. Proteins 70:83–92PubMedGoogle Scholar
  111. 111.
    Bushnell GW, Louie GV, Brayer GD (1990) High-resolution three-dimensional structure of horse heart cytochrome c. J Mol Biol 214:585–595PubMedGoogle Scholar
  112. 112.
    Louie GV, Brayer GD (1990) High-resolution refinement of yeast iso-1-cytochrome c and comparisons with other eukaryotic cytochromes c. J Mol Biol 214:527–555PubMedGoogle Scholar
  113. 113.
    Ptitsyn OB (1998) Protein folding and protein evolution: common folding nucleus in different subfamilies of c-type cytochromes? J Mol Biol 278:655–666PubMedGoogle Scholar
  114. 114.
    Fersht AR (1997) Nucleation mechanisms in protein folding. Curr Opin Struct Biol 7:3–9PubMedGoogle Scholar
  115. 115.
    Colon W, Elove GA, Wakem LP et al (1996) Side chain packing of the N- and C-terminal helices plays a critical role in the kinetics of cytochrome c folding. Biochemistry 35:5538–5549PubMedGoogle Scholar
  116. 116.
    Roder H, Colon W (1997) Kinetic role of early intermediates in protein folding. Curr Opin Struct Biol 7:15–28PubMedGoogle Scholar
  117. 117.
    Marmorino JL, Pielak GJ (1995) A native tertiary interaction stabilizes the a state of cytochrome c. Biochemistry 34:3140–3143PubMedGoogle Scholar
  118. 118.
    Matthews BW (1993) Structural and genetic analysis of protein stability. Annu Rev Biochem 62:139–160PubMedGoogle Scholar
  119. 119.
    Takeda T, Sonoyama T, Takayama SJ et al (2009) Correlation between the stability and redox potential of three homologous cytochromes c from two thermophiles and one mesophile. Biosci Biotechnol Biochem 73:366–371PubMedGoogle Scholar
  120. 120.
    Terui N, Tachiiri N, Matsuo H et al (2003) Relationship between redox function and protein stability of cytochromes c. J Am Chem Soc 125:13650–13651PubMedGoogle Scholar
  121. 121.
    Herbaud ML, Aubert C, Durand MC et al (2000) Escherichia coli is able to produce heterologous tetraheme cytochrome c(3) when the ccm genes are co-expressed. Biochim Biophys Acta 1481:18–24PubMedGoogle Scholar
  122. 122.
    Pettigrew GW, Leaver JL, Meyer TE, Ryle AP (1975) Purification, properties and amino acid sequence of atypical cytochrome c from two protozoa, Euglena gracilis and Crithidia oncopelti. Biochem J 147:291–302PubMedGoogle Scholar
  123. 123.
    Priest JW, Hajduk SL (1992) Cytochrome c reductase purified from Crithidia fasciculata contains an atypical cytochrome c1. J Biol Chem 267:20188–20195PubMedGoogle Scholar
  124. 124.
    Rios-Velazquez C, Cox RL, Donohue TJ (2001) Characterization of Rhodobacter sphaeroides cytochrome c(2) proteins with altered heme attachment sites. Arch Biochem Biophys 389:234–244PubMedGoogle Scholar
  125. 125.
    Barker PD, Ferguson SJ (1999) Still a puzzle: why is haem covalently attached in c-type cytochromes? Structure 7:R281–R290PubMedGoogle Scholar
  126. 126.
    Thony-Meyer L (2000) Haem-polypeptide interactions during cytochrome c maturation. Biochim Biophys Acta 1459:316–324PubMedGoogle Scholar
  127. 127.
    Stellwagen E, Cass R (1974) Alkaline isomerization of ferricytochrome C from Euglena gracilis. Biochem Biophys Res Commun 60:371–375PubMedGoogle Scholar
  128. 128.
    Bowman SE, Bren KL (2008) The chemistry and biochemistry of heme c: functional bases for covalent attachment. Nat Prod Rep 25:1118–1130PubMedCentralPubMedGoogle Scholar
  129. 129.
    Hampsey DM, Das G, Sherman F (1988) Yeast iso-1-cytochrome c: genetic analysis of structural requirements. FEBS Lett 231:275–283PubMedGoogle Scholar
  130. 130.
    Rosell FI, Mauk AG (2002) Spectroscopic properties of a mitochondrial cytochrome C with a single thioether bond to the heme prosthetic group. Biochemistry 41:7811–7818PubMedGoogle Scholar
  131. 131.
    Hennig B, Neupert W (1983) Biogenesis of cytochrome c in Neurospora crassa. Methods Enzymol 97:261–274PubMedGoogle Scholar
  132. 132.
    Dumont MD, Mathews AJ, Nall BT et al (1990) Differential stability of two apo-isocytochromes c in the yeast Saccharomyces cerevisiae. J Biol Chem 265:2733–2739PubMedGoogle Scholar
  133. 133.
    Wang X, Dumont ME, Sherman F (1996) Sequence requirements for mitochondrial import of yeast cytochrome c. J Biol Chem 271:6594–6604PubMedGoogle Scholar
  134. 134.
    Mavridou DA, Stevens JM, Monkemeyer L et al (2012) A pivotal heme-transfer reaction intermediate in cytochrome c biogenesis. J Biol Chem 287:2342–2352PubMedGoogle Scholar
  135. 135.
    Cowley AB, Lukat-Rodgers GS, Rodgers KR, Benson DR (2004) A possible role for the covalent heme-protein linkage in cytochrome c revealed via comparison of N-acetylmicroperoxidase-8 and a synthetic, monohistidine-coordinated heme peptide. Biochemistry 43:1656–1666PubMedGoogle Scholar
  136. 136.
    Dumont ME, Corin AF, Campbell GA (1994) Noncovalent binding of heme induces a compact apocytochrome c structure. Biochemistry 33:7368–7378PubMedGoogle Scholar
  137. 137.
    Kang X, Carey J (1999) Role of heme in structural organization of cytochrome c probed by semisynthesis. Biochemistry 38:15944–15951PubMedGoogle Scholar
  138. 138.
    Lu Y, Casimiro DR, Bren KL et al (1993) Structurally engineered cytochromes with unusual ligand-binding properties: expression of Saccharomyces cerevisiae Met-80–> Ala iso-1-cytochrome c. Proc Natl Acad Sci USA 90:11456–11459PubMedGoogle Scholar
  139. 139.
    Raphael AL (1991) Semisynthesis of Axial-Ligand (position 80) mutants of cytochrome c. J Am Chem Soc 82:1038–1040Google Scholar
  140. 140.
    Rux JJ, Dawson JH (1991) Magnetic circular dichroism spectroscopy as a probe of axial heme ligand replacement in semisynthetic mutants of cytochrome c. FEBS Lett 290:49–51PubMedGoogle Scholar
  141. 141.
    Silkstone G, Jasaitis A, Wilson MT, Vos MH (2007) Ligand dynamics in an electron transfer protein. Picosecond geminate recombination of carbon monoxide to heme in mutant forms of cytochrome c. J Biol Chem 282:1638–1649PubMedGoogle Scholar
  142. 142.
    Silkstone G, Stanway G, Brzezinski P, Wilson MT (2002) Production and characterisation of Met80X mutants of yeast iso-1-cytochrome c: spectral, photochemical and binding studies on the ferrous derivatives. Biophys Chem 98:65–77PubMedGoogle Scholar
  143. 143.
    Bagel ova J, Gazova Z, Valusova E, Antalik M (2001) Conformational stability of ferricytochrome c near the heme in its complex with heparin in alkaline pH. Carbohydr Polym 135:980–986Google Scholar
  144. 144.
    Banci L, Bertini I, Bren KL et al (1995) Three-dimensional solution structure of the cyanide adduct of a Met80Ala variant of Saccharomyces cerevisiae iso-1-cytochrome c. Identification of ligand-residue interactions in the distal heme cavity. Biochemistry 34:11385–11398PubMedGoogle Scholar
  145. 145.
    Satoh T, Itoga A, Isogai Y et al (2002) Increasing the conformational stability by replacement of heme axial ligand in c-type cytochrome. FEBS Lett 531:543–547PubMedGoogle Scholar
  146. 146.
    Yeh SR, Takahashi S, Fan B, Rousseau DL (1997) Ligand exchange during cytochrome c folding. Nat Struct Biol 4:51–56PubMedGoogle Scholar
  147. 147.
    Elove GA, Bhuyan AK, Roder H (1994) Kinetic mechanism of cytochrome c folding: involvement of the heme and its ligands. Biochemistry 33:6925–6935PubMedGoogle Scholar
  148. 148.
    Hagen SJ, Latypov RF, Dolgikh DA, Roder H (2002) Rapid intrachain binding of histidine-26 and histidine-33 to heme in unfolded ferrocytochrome C. Biochemistry 41:1372–1380PubMedGoogle Scholar
  149. 149.
    Takano T, Dickerson RE (1981) Conformation change of cytochrome c. I. Ferrocytochrome c structure refined at 1.5 Å resolution. J Mol Biol 153:79–94PubMedGoogle Scholar
  150. 150.
    Dyson HJ, Beattie JK (1982) Spin state and unfolding equilibria of ferricytochrome c in acidic solutions. J Biol Chem 257:2267–2273PubMedGoogle Scholar
  151. 151.
    Greenwood C, Palmer G (1965) Evidence for the existence of two functionally distinct forms cytochrome c manomer at alkaline pH. J Biol Chem 240:3660–3663PubMedGoogle Scholar
  152. 152.
    Schejter A, George P (1964) The 695-nm band of ferricytochrome C and its relationship to protein conformation. Biochemistry 3:1045–1049PubMedGoogle Scholar
  153. 153.
    Wallace CJ, Clark-Lewis I (1992) Functional role of heme ligation in cytochrome c. Effects of replacement of methionine 80 with natural and non-natural residues by semisynthesis. J Biol Chem 267:3852–3861PubMedGoogle Scholar
  154. 154.
    George P, Glauser SC, Schejter A (1967) The reactivity of ferricytochrome c with ionic ligands. J Biol Chem 242:1690–1695PubMedGoogle Scholar
  155. 155.
    Babul J, Stellwagen E (1971) The existence of heme-protein coordinate-covalent bonds in denaturing solvents. Biopolymers 10:2359–2361PubMedGoogle Scholar
  156. 156.
    Muthukrishnan K, Nall BT (1991) Effective concentrations of amino acid side chains in an unfolded protein. Biochemistry 30:4706–4710PubMedGoogle Scholar
  157. 157.
    Stellwagen E, Rysavy R, Babul G (1972) The conformation of horse heart apocytochrome c. J Biol Chem 247:8074–8077PubMedGoogle Scholar
  158. 158.
    Tsong TY (1975) An acid induced conformational transition of denatured cytochrome c in urea and guanidine hydrochloride solutions. Biochemistry 14:1542–1547PubMedGoogle Scholar
  159. 159.
    Droghetti E, Oellerich S, Hildebrandt P, Smulevich G (2006) Heme coordination states of unfolded ferrous cytochrome C. Biophys J 91:3022–3031PubMedCentralPubMedGoogle Scholar
  160. 160.
    Cutler RL, Pielak GJ, Mauk AG, Smith M (1987) Replacement of cysteine-107 of Saccharomyces cerevisiae iso-1-cytochrome c with threonine: improved stability of the mutant protein. Protein Eng 1:95–99PubMedGoogle Scholar
  161. 161.
    Allen JW, Ferguson SJ (2003) 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 375:721–728PubMedGoogle Scholar
  162. 162.
    Allen JW, Leach N, Ferguson SJ (2005) 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 389:587–592PubMedGoogle Scholar
  163. 163.
    Bowman SE, Bren KL (2010) Variation and analysis of second-sphere interactions and axial histidinate character in c-type cytochromes. Inorg Chem 49:7890–7897PubMedCentralPubMedGoogle Scholar
  164. 164.
    Garcia-Rubio I, Braun M, Gromov I et al (2007) Axial coordination of heme in ferric CcmE chaperone characterized by EPR spectroscopy. Biophys J 92:1361–1373PubMedCentralPubMedGoogle Scholar
  165. 165.
    Takahashi A, Kurahashi T, Fujii H (2009) Effect of imidazole and phenolate axial ligands on the electronic structure and reactivity of oxoiron(IV) porphyrin pi-cation radical complexes: drastic increase in oxo-transfer and hydrogen abstraction reactivities. Inorg Chem 48:2614–2625PubMedGoogle Scholar
  166. 166.
    Fumo G, Spitzer JS, Fetrow JS (1995) A method of directed random mutagenesis of the yeast chromosome shows that the iso-1-cytochrome c heme ligand His18 is essential. Gene 164:33–39PubMedGoogle Scholar
  167. 167.
    Yeh SR, Rousseau DL (1999) Ligand exchange during unfolding of cytochrome c. J Biol Chem 274:17853–17859PubMedGoogle Scholar
  168. 168.
    Casalini S, Battistuzzi G, Borsari M et al (2010) Electron transfer properties and hydrogen peroxide electrocatalysis of cytochrome c variants at positions 67 and 80. J Phys Chem B 114:1698–1706PubMedGoogle Scholar
  169. 169.
    Senn H, Wuthrich K (1985) Amino acid sequence, haem-iron co-ordination geometry and functional properties of mitochondrial and bacterial c-type cytochromes. Q Rev Biophys 18:111–134PubMedGoogle Scholar
  170. 170.
    Raphael AL, Gray HB (1989) Axial ligand replacement in horse heart cytochrome c by semisynthesis. Proteins 6:338–340PubMedGoogle Scholar
  171. 171.
    Battistuzzi G, Bortolotti CA, Bellei M et al (2012) Role of Met80 and Tyr67 in the low-pH conformational equilibria of cytochrome c. Biochemistry 51:5967–5978PubMedGoogle Scholar
  172. 172.
    Ferri T, Poscia A, Ascoli F, Santucci R (1996) Direct electrochemical evidence for an equilibrium intermediate in the guanidine-induced unfolding of cytochrome c. Biochim Biophys Acta 1298:102–108PubMedGoogle Scholar
  173. 173.
    Santucci R, Brunori M, Ascoli F (1987) Unfolding and flexibility in hemoproteins shown in the case of carboxymethylated cytochrome c. Biochim Biophys Acta 914:185–189PubMedGoogle Scholar
  174. 174.
    Santucci R, Giartosio A, Ascoli F (1989) Structural transitions of carboxymethylated cytochrome c: calorimetric and circular dichroic studies. Arch Biochem Biophys 275:496–504PubMedGoogle Scholar
  175. 175.
    Bren KL, Gray HB (1993) Structurally engineered cytochromes with novel ligand binding sites: oxy and carbon monoxy derivatives of semisynthetic horse heart Ala80 cytochrome c. J Am Chem Soc 115:10382Google Scholar
  176. 176.
    Brunori M, Wilson MT, Antonini E (1972) Properties of modified cytochromes. I. Equilibrium and kinetics of the pH-dependent transition in carboxymethylated horse heart cytochrome c. J Biol Chem 247:6076–6081PubMedGoogle Scholar
  177. 177.
    Wilson MT, Brunori M, Rotilio GC, Antonini E (1973) Properties of modified cytochromes. II. Ligand binding to reduced carboxymethyl cytochrome c. J Biol Chem 248:8162–8169PubMedGoogle Scholar
  178. 178.
    Flynn PF, Bieber Urbauer RJ, Zhang H et al (2001) Main chain and side chain dynamics of a heme protein: 15N and 2H NMR relaxation studies of R. capsulatus ferrocytochrome c2. Biochemistry 40:6559–6569PubMedGoogle Scholar
  179. 179.
    Casalini S, Battistuzzi G, Borsari M et al (2008) Electron transfer and electrocatalytic properties of the immobilized methionine80alanine cytochrome c variant. J Phys Chem B 112:1555–1563PubMedGoogle Scholar
  180. 180.
    Indiani C, de Sanctis G, Neri F et al (2000) Effect of pH on axial ligand coordination of cytochrome c” from Methylophilus methylotrophus and horse heart cytochrome c. Biochemistry 39:8234–8242PubMedGoogle Scholar
  181. 181.
    Mathews FS (1985) The structure, function and evolution of cytochromes. Prog Biophys Mol Biol 45:1–56PubMedGoogle Scholar
  182. 182.
    Auld DS, Young GB, Saunders AJ et al (1993) Probing weakly polar interactions in cytochrome c. Protein Sci 2:2187–2197PubMedGoogle Scholar
  183. 183.
    Gao Y, Boyd J, Williams RJ, Pielak GJ (1990) Assignment of proton resonances, identification of secondary structural elements, and analysis of backbone chemical shifts for the C102T variant of yeast iso-1-cytochrome c and horse cytochrome c. Biochemistry 29:6994–7003PubMedGoogle Scholar
  184. 184.
    Roder H, Elove GA, Englander SW (1988) Structural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR. Nature 335:700–704PubMedCentralPubMedGoogle Scholar
  185. 185.
    Efimov AV (1984) A novel super-secondary structure of proteins and the relation between the structure and the amino acid sequence. FEBS Lett 166:33–38PubMedGoogle Scholar
  186. 186.
    Richardson JS, Richardson DC (1988) Helix lap-joints as ion-binding sites: DNA-binding motifs and Ca-binding “EF hands” are related by charge and sequence reversal. Proteins 4:229–239PubMedGoogle Scholar
  187. 187.
    Pielak GJ, Auld DS, Beasley JR et al (1995) Protein thermal denaturation, side-chain models, and evolution: amino acid substitutions at a conserved helix-helix interface. Biochemistry 34:3268–3276PubMedGoogle Scholar
  188. 188.
    Auld DS, Pielak GJ (1991) Constraints on amino acid substitutions in the N-terminal helix of cytochrome c explored by random mutagenesis. Biochemistry 30:8684–8690PubMedGoogle Scholar
  189. 189.
    Pelletier H, Kraut J (1992) Crystal structure of a complex between electron transfer partners, cytochrome c peroxidase and cytochrome c. Science 258:1748–1755PubMedGoogle Scholar
  190. 190.
    Sosnick TR, Mayne L, Hiller R, Englander SW (1994) The barriers in protein folding. Nat Struct Biol 1:149–156PubMedGoogle Scholar
  191. 191.
    Wu LC, Laub PB, Elove GA et al (1993) A noncovalent peptide complex as a model for an early folding intermediate of cytochrome c. Biochemistry 32:10271–10276PubMedGoogle Scholar
  192. 192.
    Berghuis AM, Brayer GD (1992) Oxidation state-dependent conformational changes in cytochrome c. J Mol Biol 223:959–976PubMedGoogle Scholar
  193. 193.
    Beasley JR, Pielak GJ (1996) Requirements for perpendicular helix pairing. Proteins 26:95–107PubMedGoogle Scholar
  194. 194.
    Gochin M, Roder H (1995) Protein structure refinement based on paramagnetic NMR shifts: applications to wild-type and mutant forms of cytochrome c. Protein Sci 4:296–305PubMedGoogle Scholar
  195. 195.
    Amegadzie BY, Zitomer RS, Hollenberg CP (1990) Characterization of the cytochrome c gene from the starch-fermenting yeast Schwanniomyces occidentalis and its expression in Baker’s yeast. Yeast 6:429–440PubMedGoogle Scholar
  196. 196.
    Vanfleteren JR, Evers EA, Van de Werken G, Van Beeumen JJ (1990) The primary structure of cytochrome c from the nematode Caenorhabditis elegans. Biochem J 271:613–620PubMedGoogle Scholar
  197. 197.
    Lyu PC, Liff MI, Marky LA, Kallenbach NR (1990) Side chain contributions to the stability of alpha-helical structure in peptides. Science 250:669–673PubMedGoogle Scholar
  198. 198.
    Padmanabhan S, Marqusee S, Ridgeway T et al (1990) Relative helix-forming tendencies of nonpolar amino acids. Nature 344:268–270PubMedGoogle Scholar
  199. 199.
    O’Neil KT, DeGrado WF (1990) A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. Science 250:646–651PubMedGoogle Scholar
  200. 200.
    Richardson JS, Richardson DC (1988) Amino acid preferences for specific locations at the ends of alpha helices. Science 240:1648–1652PubMedGoogle Scholar
  201. 201.
    Chothia C, Lesk AM (1985) Helix movements and the reconstruction of the haem pocket during the evolution of the cytochrome c family. J Mol Biol 182:151–158PubMedGoogle Scholar
  202. 202.
    Burley SK, Petsko GA (1988) Weakly polar interactions in proteins. Adv Protein Chem 39:125–189PubMedGoogle Scholar
  203. 203.
    Serrano L, Bycroft M, Fersht AR (1991) Aromatic-aromatic interactions and protein stability. Investigation by double-mutant cycles. J Mol Biol 218:465–475PubMedGoogle Scholar
  204. 204.
    Kleingardner JG, Bren KL (2011) Comparing substrate specificity between cytochrome c maturation and cytochrome c heme lyase systems for cytochrome c biogenesis. Metallomics 3:396–403PubMedCentralPubMedGoogle Scholar
  205. 205.
    Lee I, Salomon AR, Yu K et al (2006) New prospects for an old enzyme: mammalian cytochrome c is tyrosine-phosphorylated in vivo. Biochemistry 45:9121–9128PubMedGoogle Scholar
  206. 206.
    Garcia-Heredia JM, Diaz-Quintana A, Salzano M et al (2011) Tyrosine phosphorylation turns alkaline transition into a biologically relevant process and makes human cytochrome c behave as an anti-apoptotic switch. J Biol Inorg Chem 16:1155–1168PubMedGoogle Scholar
  207. 207.
    Creighton TE (1983) An empirical approach to protein conformation stability and flexibility. Biopolymers 22:49–58PubMedGoogle Scholar
  208. 208.
    Shortle D, Lin B (1985) Genetic analysis of staphylococcal nuclease: identification of three intragenic “global” suppressors of nuclease-minus mutations. Genetics 110:539–555PubMedGoogle Scholar
  209. 209.
    Das G, Hickey DR, McLendon D et al (1989) Dramatic thermostabilization of yeast iso-1-cytochrome c by an asparagine—isoleucine replacement at position 57. Proc Natl Acad Sci USA 86:496–499PubMedGoogle Scholar
  210. 210.
    Schweingruber ME, Stewart JW, Sherman F (1979) Primary site and second site revertants of missense mutants of the evolutionarily invariant tryptophan 64 in iso-1-cytochrome c from yeast. J Biol Chem 254:4132–4143PubMedGoogle Scholar
  211. 211.
    Goto Y, Calciano LJ, Fink AL (1990) Acid-induced folding of proteins. Proc Natl Acad Sci USA 87:573–577PubMedGoogle Scholar
  212. 212.
    Potekhin S, Pfeil W (1989) Microcalorimetric studies of conformational transitions of ferricytochrome c in acidic solution. Biophys Chem 34:55–62PubMedGoogle Scholar
  213. 213.
    Stellwagen E, Babul J (1975) Stabilization of the globular structure of ferricytochrome c by chloride in acidic solvents. Biochemistry 14:5135–5140PubMedGoogle Scholar
  214. 214.
    Nakamura S, Baba T, Kidokoro S (2007) A molten globule-like intermediate state detected in the thermal transition of cytochrome c under low salt concentration. Biophys Chem 127:103–112PubMedGoogle Scholar
  215. 215.
    Nakamura S, Kidokoro S (2005) Direct observation of the enthalpy change accompanying the native to molten-globule transition of cytochrome c by using isothermal acid-titration calorimetry. Biophys Chem 113:161–168PubMedGoogle Scholar
  216. 216.
    Sinibaldi F, Howes BD, Smulevich G et al (2003) Anion concentration modulates the conformation and stability of the molten globule of cytochrome c. J Biol Inorg Chem 8:663–670PubMedGoogle Scholar
  217. 217.
    Sinibaldi F, Piro MC, Howes BD et al (2003) Rupture of the hydrogen bond linking two Omega-loops induces the molten globule state at neutral pH in cytochrome c. Biochemistry 42:7604–7610PubMedGoogle Scholar
  218. 218.
    Uversky VN, Ptitsyn OB (1994) “Partly folded” state, a new equilibrium state of protein molecules: four-state guanidinium chloride-induced unfolding of beta-lactamase at low temperature. Biochemistry 33:2782–2791PubMedGoogle Scholar
  219. 219.
    Uversky VN, Ptitsyn OB (1996) Further evidence on the equilibrium “pre-molten globule state”: four-state guanidinium chloride-induced unfolding of carbonic anhydrase B at low temperature. J Mol Biol 255:215–228PubMedGoogle Scholar
  220. 220.
    Louie GV, Hutcheon WL, Brayer GD (1988) Yeast iso-1-cytochrome c. A 2.8 Å resolution three-dimensional structure determination. J Mol Biol 199:295–314PubMedGoogle Scholar
  221. 221.
    Tanaka N, Yamane T, Tsukihara T et al (1975) The crystal structure of bonito (katsuo) ferrocytochrome c at 2.3 Å resolution. II. Structure and function. J Biochem 77:147–162PubMedGoogle Scholar
  222. 222.
    Cookson DJ, Moore GR, Pitt RC et al (1978) Structural homology of cytochromes c. Eur J Biochem 83:261–275PubMedGoogle Scholar
  223. 223.
    Timkovich R, Dickerson RE (1976) The structure of Paracoccus denitrificans cytochrome c550. J Biol Chem 251:4033–4046PubMedGoogle Scholar
  224. 224.
    Tsong TY (1974) The Trp-59 fluorescence of ferricytochrome c as a sensitive measure of the over-all protein conformation. J Biol Chem 249:1988–1990PubMedGoogle Scholar
  225. 225.
    Sherman F, Stewart JW, Jackson M et al (1974) Mutants of yeast defective in iso-1-cytochrome c. Genetics 77:255–284PubMedGoogle Scholar
  226. 226.
    Lett CM, Guillemette JG (2002) Increasing the redox potential of isoform 1 of yeast cytochrome c through the modification of select haem interactions. Biochem J 362:281–287PubMedGoogle Scholar
  227. 227.
    Aviram I, Schejter A (1971) Modification of the tryptophanyl residue of horse heart cytochrome c. Biochim Biophys Acta 229:113–118PubMedGoogle Scholar
  228. 228.
    Caffrey MS, Cusanovich MA (1993) Role of the highly conserved tryptophan of cytochrome c in stability. Arch Biochem Biophys 304:205–208PubMedGoogle Scholar
  229. 229.
    Black KM, Clark-Lewis I, Wallace CJ (2001) Conserved tryptophan in cytochrome c: importance of the unique side-chain features of the indole moiety. Biochem J 359:715–720PubMedGoogle Scholar
  230. 230.
    Wallace CJ, Mascagni P, Chait BT et al (1989) Substitutions engineered by chemical synthesis at three conserved sites in mitochondrial cytochrome c. Thermodynamic and functional consequences. J Biol Chem 264:15199–15209PubMedGoogle Scholar
  231. 231.
    Brayer GD, Murphy MEP (1993) Structural studies of eukaryotic cytochromes c. The Cytochrome c HandbookGoogle Scholar
  232. 232.
    Hickey DR, Berghuis AM, Lafond G et al (1991) Enhanced thermodynamic stabilities of yeast iso-1-cytochromes c with amino acid replacements at positions 52 and 102. J Biol Chem 266:11686–11694PubMedGoogle Scholar
  233. 233.
    Luntz TL, Schejter A, Garber EA, Margoliash E (1989) Structural significance of an internal water molecule studied by site-directed mutagenesis of tyrosine-67 in rat cytochrome c. Proc Natl Acad Sci USA 86:3524–3528PubMedGoogle Scholar
  234. 234.
    Schejter A, Koshy TI, Luntz TL et al (1994) Effects of mutating Asn-52 to isoleucine on the haem-linked properties of cytochrome c. Biochem J 302(Pt 1):95–101PubMedGoogle Scholar
  235. 235.
    Schroeder HR, McOdimba FA, Guillemette JG, Kornblatt JA (1997) The polarity of tyrosine 67 in yeast iso-1-cytochrome c monitored by second derivative spectroscopy. Biochem Cell Biol 75:191–197PubMedGoogle Scholar
  236. 236.
    Berghuis AM, Guillemette JG, McLendon G et al (1994) The role of a conserved internal water molecule and its associated hydrogen bond network in cytochrome c. J Mol Biol 236:786–799PubMedGoogle Scholar
  237. 237.
    Lett CM, Berghuis AM, Frey HE et al (1996) The role of a conserved water molecule in the redox-dependent thermal stability of iso-1-cytochrome c. J Biol Chem 271:29088–29093PubMedGoogle Scholar
  238. 238.
    Berghuis AM, Guillemette JG, Smith M, Brayer GD (1994) Mutation of tyrosine-67 to phenylalanine in cytochrome c significantly alters the local heme environment. J Mol Biol 235:1326–1341PubMedGoogle Scholar
  239. 239.
    Shelnutt JA, Rousseau DL, Dethmers JK, Margoliash E (1981) Protein influences on porphyrin structure in cytochrome c: evidence from Raman difference spectroscopy. Biochemistry 20:6485–6497PubMedGoogle Scholar
  240. 240.
    Feinberg BA, Liu X, Ryan MD et al (1998) Direct voltammetric observation of redox driven changes in axial coordination and intramolecular rearrangement of the phenylalanine-82-histidine variant of yeast iso-1-cytochrome c. Biochemistry 37:13091–13101PubMedGoogle Scholar
  241. 241.
    Kassner RJ (1972) Effects of nonpolar environments on the redox potentials of heme complexes. Proc Natl Acad Sci USA 69:2263–2267PubMedGoogle Scholar
  242. 242.
    Marchon JC, Mashiko T, Reed CA (1982) How does nature control cytochrome redox potentials? In: Ho C et al (eds) Interactions between iron and proteins in oxygen and electron transport, vol 2. Elsevier, pp 67–72Google Scholar
  243. 243.
    Takano T, Dickerson RE (1981) Conformation change of cytochrome c. II. Ferricytochrome c refinement at 1.8 Å and comparison with the ferrocytochrome structure. J Mol Biol 153:95–115PubMedGoogle Scholar
  244. 244.
    Mauk AG (1991) Electron transfer in genetically engineered proteins. The cytochrome c paradigm. Struct Bond 75:131–157Google Scholar
  245. 245.
    Liang N, Pielak GJ, Mauk AG et al (1987) Yeast cytochrome c with phenylalanine or tyrosine at position 87 transfers electrons to (zinc cytochrome c peroxidase)+ at a rate ten thousand times that of the serine-87 or glycine-87 variants. Proc Natl Acad Sci USA 84:1249–1252PubMedGoogle Scholar
  246. 246.
    Liggins JR, Lo TP, Brayer GD, Nall BT (1999) Thermal stability of hydrophobic heme pocket variants of oxidized cytochrome c. Protein Sci 8:2645–2654PubMedGoogle Scholar
  247. 247.
    Lo TP, Guillemette JG, Louie GV et al (1995) Structural studies of the roles of residues 82 and 85 at the interactive face of cytochrome c. Biochemistry 34:163–171PubMedGoogle Scholar
  248. 248.
    Louie GV, Brayer GD (1989) A polypeptide chain-refolding event occurs in the Gly82 variant of yeast iso-1-cytochrome c. J Mol Biol 210:313–322PubMedGoogle Scholar
  249. 249.
    Louie GV, Pielak GJ, Smith M, Brayer GD (1988) Role of phenylalanine-82 in yeast iso-1-cytochrome c and remote conformational changes induced by a serine residue at this position. Biochemistry 27:7870–7876PubMedGoogle Scholar
  250. 250.
    Pielak GJ, Oikawa K, Mauk AG et al (1986) Elimination of the negative Soret Cotton effect of eukaryotic cytochromes c by replacement of an invariant phenylalanine residue by site-directed mutagenesis. J Am Chem Soc 108:2724–2727Google Scholar
  251. 251.
    Rafferty SP, Pearce LL, Barker PD et al (1990) Electrochemical, kinetic, and circular dichroic consequences of mutations at position 82 of yeast iso-1-cytochrome c. Biochemistry 29:9365–9369PubMedGoogle Scholar
  252. 252.
    Rosell FI, Harris TR, Hildebrand DP et al (2000) Characterization of an alkaline transition intermediate stabilized in the Phe82Trp variant of yeast iso-1-cytochrome c. Biochemistry 39:9047–9054PubMedGoogle Scholar
  253. 253.
    Torres E, Sandoval JE, Rosell FE et al (1995) Site-directed mutagenesis improves the biocatalytic activity of iso-1-cytochrome c in polycyclic hydrocarbon oxidation. Enzyme Microb Technol 99:779–781Google Scholar
  254. 254.
    Inglis SC, Guillemette JG, Johnson JA, Smith M (1991) Analysis of the invariant Phe82 residue of yeast iso-1-cytochrome c by site-directed mutagenesis using a phagemid yeast shuttle vector. Protein Eng 4:569–574PubMedGoogle Scholar
  255. 255.
    Pielak GJ, Mauk AG, Smith M (1985) Site-directed mutagenesis of cytochrome c shows that an invariant Phe is not essential for function. Nature 313:152–154PubMedGoogle Scholar
  256. 256.
    Liang N, Mauk AG, Pielak GJ et al (1988) Regulation of interprotein electron transfer by residue 82 of yeast cytochrome c. Science 240:311–313PubMedGoogle Scholar
  257. 257.
    Poulos TL, Kraut J (1980) A hypothetical model of the cytochrome c peroxidase. cytochrome c electron transfer complex. J Biol Chem 255:10322–10330PubMedGoogle Scholar
  258. 258.
    Wendoloski JJ, Matthew JB, Weber PC, Salemme FR (1987) Molecular dynamics of a cytochrome c-cytochrome b5 electron transfer complex. Science 238:794–797PubMedGoogle Scholar
  259. 259.
    Pearce LL, Gartner AL, Smith M, Mauk AG (1989) Mutation-induced perturbation of the cytochrome c alkaline transition. Biochemistry 28:3152–3156PubMedGoogle Scholar
  260. 260.
    Ochi H, Hata Y, Tanaka N et al (1983) Structure of rice ferricytochrome c at 2.0 Å resolution. J Mol Biol 166:407–418PubMedGoogle Scholar
  261. 261.
    Pielak GJ, Concar DW, Moore GR, Williams RJ (1987) The structure of cytochrome c and its relation to recent studies of long-range electron transfer. Protein Eng 1:83–88PubMedGoogle Scholar
  262. 262.
    Greene RM, Betz SF, Hilgen-Willis S et al (1993) Changes in global stability and local structure of cytochrome c upon substituting phenylalanine-82 with tyrosine. J Inorg Biochem 51:663–676PubMedGoogle Scholar
  263. 263.
    Lum VR, Brayer GD, Louie GV et al (1987) Protein Struct. Fold Design 26:143–150Google Scholar
  264. 264.
    Dickerson RE (1980) Cytochrome c and the evolution of energy metabolism. Sci Am 242:137–153PubMedGoogle Scholar
  265. 265.
    Summers MR, McPhie P (1972) The mechanism of unfolding of globular proteins. Biochem Biophys Res Commun 47:831–837PubMedGoogle Scholar
  266. 266.
    Tsong TY (1973) Detection of three kinetic phases in the thermal unfolding of ferricytochrome c. Biochemistry N10I:2209–2214Google Scholar
  267. 267.
    Brandts JF, Halvorson HR, Brennan M (1975) Consideration of the Possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues. Biochemistry 14:4953–4963PubMedGoogle Scholar
  268. 268.
    Ramdas L, Nall BT (1986) Folding/unfolding kinetics of mutant forms of iso-1-cytochrome c with replacement of proline-71. Biochemistry 25:6959–6964PubMedGoogle Scholar
  269. 269.
    White TB, Berget PB, Nall BT (1987) Changes in conformation and slow refolding kinetics in mutant iso-2-cytochrome c with replacement of a conserved proline residue. Biochemistry 26:4358–4366PubMedGoogle Scholar
  270. 270.
    Koshy TI, Luntz TL, Schejter A, Margoliash E (1990) Changing the invariant proline-30 of rat and Drosophila melanogaster cytochromes c to alanine or valine destabilizes the heme crevice more than the overall conformation. Proc Natl Acad Sci USA 87:8697–8701PubMedGoogle Scholar
  271. 271.
    George P, Lyster RL (1958) Crevice structures in hemoprotein reactions. Proc Natl Acad Sci USA 44:1013–1029PubMedGoogle Scholar
  272. 272.
    Baistrocchi P, Banci L, Bertini I et al (1996) Three-dimensional solution structure of Saccharomyces cerevisiae reduced iso-1-cytochrome c. Biochemistry 35:13788–13796PubMedGoogle Scholar
  273. 273.
    Kellis JT Jr, Nyberg K, Sali D, Fersht AR (1988) Contribution of hydrophobic interactions to protein stability. Nature 333:784–786PubMedGoogle Scholar
  274. 274.
    Poerio E, Parr GR, Taniuchi H (1986) A study of roles of evolutionarily invariant proline 30 and glycine 34 of cytochrome c. J Biol Chem 261:10976–10989PubMedGoogle Scholar
  275. 275.
    Wood LC, Muthukrishnan K, White TB et al (1988) Construction and characterization of mutant iso-2-cytochromes c with replacement of conserved prolines. Biochemistry 27:8554–8561PubMedGoogle Scholar
  276. 276.
    Gooley PR, MacKenzie NE (1990) Pro—Ala-35 Rhodobacter capsulatus cytochrome c2 shows dynamic not structural differences. A 1H and 15N NMR study. FEBS Lett 260:225–228PubMedGoogle Scholar
  277. 277.
    Lan W, Wang Z, Yang Z et al (2011) Conformational toggling of yeast iso-1-cytochrome C in the oxidized and reduced states. PLoS ONE 6:e27219PubMedCentralPubMedGoogle Scholar
  278. 278.
    Ernst JF, Hampsey DM, Stewart JW et al (1985) Substitutions of proline 76 in yeast iso-1-cytochrome c. Analysis of residues compatible and incompatible with folding requirements. J Biol Chem 260:13225–13236PubMedGoogle Scholar
  279. 279.
    Wallace CJA, Lewis IC (1997) A rationale for the absolute conservation of Asn 70 and pro in mitochondrial cytochromes c suggested by protein engineering. Biochemistry 39:395–399Google Scholar
  280. 280.
    Ernst JF, Stewart JW, Sherman F (1981) The cyc1-11 mutation in yeast reverts by recombination with a nonallelic gene: composite genes determining the iso-cytochromes c. Proc Natl Acad Sci USA 78:6334–6338PubMedGoogle Scholar
  281. 281.
    Ramdas L, Sherman F, Nall BT (1986) Guanidine hydrochloride induced equilibrium unfolding of mutant forms of iso-1-cytochrome c with replacement of proline-71. Biochemistry 25:6952–6958PubMedGoogle Scholar
  282. 282.
    Wood LC, White TB, Ramdas L, Nall BT (1988) Replacement of a conserved proline eliminates the absorbance-detected slow folding phase of iso-2-cytochrome c. Biochemistry 27:8562–8568PubMedGoogle Scholar
  283. 283.
    Murphy MEP (1993) Ph.D. Dissertation, University of British ColumbiaGoogle Scholar
  284. 284.
    Wuttke DS, Gray HB (1993) Protein engineering as a tool for understanding electron transfer. Curr Opin Struct Biol 3:555–563Google Scholar
  285. 285.
    Mulligan-Pullyblank P, Spitzer JS, Gilden BM, Fetrow JS (1996) Loop replacement and random mutagenesis of omega-loop D, residues 70–84, in iso-1-cytochrome c. J Biol Chem 271:8633–8645PubMedGoogle Scholar
  286. 286.
    Black KM, Wallace CJ (2007) Probing the role of the conserved beta-II turn Pro-76/Gly-77 of mitochondrial cytochrome c. Biochem Cell Biol 85:366–374PubMedGoogle Scholar
  287. 287.
    Fetrow JS, Spitzer JS, Gilden BM et al (1998) Structure, function, and temperature sensitivity of directed, random mutants at proline 76 and glycine 77 in omega-loop D of yeast iso-1-cytochrome c. Biochemistry 37:2477–2487PubMedGoogle Scholar
  288. 288.
    Ahmed AJ, Smith HT, Smith MB, Millett FS (1978) Effect of specific lysine modification on the reduction of cytochrome c by succinate-cytochrome c reductase. Biochemistry 17:2479–2483PubMedGoogle Scholar
  289. 289.
    Ferguson-Miller S, Brautigan DL, Margoliash E (1978) Definition of cytochrome c binding domains by chemical modification. III. Kinetics of reaction of carboxydinitrophenyl cytochromes c with cytochrome c oxidase. J Biol Chem 253:149–159PubMedGoogle Scholar
  290. 290.
    Koppenol WH, Margoliash E (1982) The asymmetric distribution of charges on the surface of horse cytochrome c. Functional implications. J Biol Chem 257:4426–4437PubMedGoogle Scholar
  291. 291.
    Rieder R, Bosshard HR (1978) The cytochrome c oxidase binding site on cytochrome c. Differential chemical modification of lysine residues in free and oxidase-bound cytochrome c. J Biol Chem 253:6045–6053PubMedGoogle Scholar
  292. 292.
    DeLange RJ, Glazer AN, Smith EL (1970) Identification and location of episilon-N-trimethyllysine in yeast cytochromes c. J Biol Chem 245:3325–3327PubMedGoogle Scholar
  293. 293.
    Paik WK, Cho YB, Frost B, Kim S (1989) Cytochrome c methylation. Biochem Cell Biol 67:602–611PubMedGoogle Scholar
  294. 294.
    Takakura H, Yamamoto T, Sherman F (1997) Sequence requirement for trimethylation of yeast cytochrome c. Biochemistry 36:2642–2648PubMedGoogle Scholar
  295. 295.
    Holzschu D, Principio L, Conklin KT et al (1987) Replacement of the invariant lysine 77 by arginine in yeast iso-1-cytochrome c results in enhanced and normal activities in vitro and in vivo. J Biol Chem 262:7125–7131PubMedGoogle Scholar
  296. 296.
    Sharonov GV, Feofanov AV, Bocharova OV et al (2005) Comparative analysis of proapoptotic activity of cytochrome c mutants in living cells. Apoptosis 10:797–808PubMedGoogle Scholar
  297. 297.
    Kluck RM, Ellerby LM, Ellerby HM et al (2000) Determinants of cytochrome c pro-apoptotic activity. The role of lysine 72 trimethylation. J Biol Chem 275:16127–16133PubMedGoogle Scholar
  298. 298.
    Polastro E, Looze Y, Leonis J (1976) Evidence that trimethylation of iso-1-cytochrome c from Saccharomyces cerevisiae does not alter its functional properties [proceedings]. Arch Int Physiol Biochim 84:1099–1100PubMedGoogle Scholar
  299. 299.
    Polastro E, Looze Y, Leonis J (1976) Study of the biological significance of cytochrome methylation. I. Thermal, acid and guanidinium hydrochloride denaturations of baker’s yeast ferricytochromes c. Biochim Biophys Acta 446:310–320PubMedGoogle Scholar
  300. 300.
    Polastro E, Looze Y, Leonis J (1976) Study of the biological significance of the methylation of cytochromes c. I. Thermal, acid and guanidinium hydrochloride denaturations of baker’s yeast ferricytochromes c. Arch Int Physiol Biochim 84:407–409PubMedGoogle Scholar
  301. 301.
    Polastro ET, Deconinck MM, Devogel MR et al (1978) Evidence that trimethylation of iso-I-cytochrome c from Saccharomyces cerevisiae affects interaction with the mitochondrion. FEBS Lett 86:17–20PubMedGoogle Scholar
  302. 302.
    Guiard B, Lederer F (1979) The “cytochrome b5 fold”: structure of a novel protein superfamily. J Mol Biol 135:639–650PubMedGoogle Scholar
  303. 303.
    Paik WK, Polastro E, Kim S (1980) Cytochrome c methylation: enzymology and biologic significance. Curr Top Cell Regul 16:87–111PubMedGoogle Scholar
  304. 304.
    Frost B, Park KS, Kim S, Paik WK (1989) Effect of enzymatic methylation of apocytochrome c on holocytochrome c formation and proteolysis. Int J Biochem 21:1407–1414PubMedGoogle Scholar
  305. 305.
    Li P, Nijhawan D, Budihardjo I et al (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489PubMedGoogle Scholar
  306. 306.
    Liu X, Kim CN, Yang J et al (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157PubMedGoogle Scholar
  307. 307.
    Rodrigues J, Lazebnic Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13:3179–3184Google Scholar
  308. 308.
    Chertkova RV, Sharonov GV, Feofanov AV et al (2008) Proapoptotic activity of cytochrome c in living cells: effect of K72 substitutions and species differences. Mol Cell Biochem 314:85–93PubMedGoogle Scholar
  309. 309.
    Yu T, Wang X, Purring-Koch C et al (2001) A mutational epitope for cytochrome C binding to the apoptosis protease activation factor-1. J Biol Chem 276:13034–13038PubMedGoogle Scholar
  310. 310.
    Cortese JD, Voglino AL, Hackenbrock CR (1998) Multiple conformations of physiological membrane-bound cytochrome c. Biochemistry 37:6402–6409PubMedGoogle Scholar
  311. 311.
    Heimburg T, Marsh D (1995) Protein surface-distribution and protein-protein interactions in the binding of peripheral proteins to charged lipid membranes. Biophys J 68:536–546PubMedCentralPubMedGoogle Scholar
  312. 312.
    Nicholls P (1974) Cytochrome c binding to enzymes and membranes. Biochim Biophys Acta 346:261–310PubMedGoogle Scholar
  313. 313.
    Pinheiro TJ, Elove GA, Watts A, Roder H (1997) Structural and kinetic description of cytochrome c unfolding induced by the interaction with lipid vesicles. Biochemistry 36:13122–13132PubMedGoogle Scholar
  314. 314.
    Pinheiro TJ, Watts A (1994) Lipid specificity in the interaction of cytochrome c with anionic phospholipid bilayers revealed by solid-state 31P NMR. Biochemistry 33:2451–2458PubMedGoogle Scholar
  315. 315.
    Soussi B, Bylund-Fellenius AC, Schersten T, Angstrom J (1990) 1H-n.m.r. evaluation of the ferricytochrome c-cardiolipin interaction. Effect of superoxide radicals. Biochem J 265:227–232PubMedGoogle Scholar
  316. 316.
    Zhang F, Rowe ES (1994) Calorimetric studies of the interactions of cytochrome c with dioleoylphosphatidylglycerol extruded vesicles: ionic strength effects. Biochim Biophys Acta 1193:219–225PubMedGoogle Scholar
  317. 317.
    Dickerson RE, Timkovich R (1975) The Enzymes (Boyer, P. D., ed), vol 11. Academic Press, Orlando, pp 397–547Google Scholar
  318. 318.
    Yu H, Lee I, Salomon AR et al (2008) Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration. Biochim Biophys Acta 1777:1066–1071PubMedCentralPubMedGoogle Scholar
  319. 319.
    Ischiropoulos H (2003) Biological selectivity and functional aspects of protein tyrosine nitration. Biochem Biophys Res Commun 305:776–783PubMedGoogle Scholar
  320. 320.
    Ischiropoulos H (2009) Protein tyrosine nitration–an update. Arch Biochem Biophys 484:117–121PubMedGoogle Scholar
  321. 321.
    Souza JM, Castro L, Cassina AM et al (2008) Nitrocytochrome c: synthesis, purification, and functional studies. Methods Enzymol 441:197–215PubMedGoogle Scholar
  322. 322.
    Batthyany C, Souza JM, Duran R et al (2005) Time course and site(s) of cytochrome c tyrosine nitration by peroxynitrite. Biochemistry 44:8038–8046PubMedGoogle Scholar
  323. 323.
    Cassina AM, Hodara R, Souza JM et al (2000) Cytochrome c nitration by peroxynitrite. J Biol Chem 275:21409–21415PubMedGoogle Scholar
  324. 324.
    Jang B, Han S (2006) Biochemical properties of cytochrome c nitrated by peroxynitrite. Biochimie 88:53–58PubMedGoogle Scholar
  325. 325.
    MacMillan-Crow LA, Cruthirds DL, Ahki KM et al (2001) Mitochondrial tyrosine nitration precedes chronic allograft nephropathy. Free Radic Biol Med 31:1603–1608PubMedGoogle Scholar
  326. 326.
    Nakagawa H, Komai N, Takusagawa M et al (2007) Nitration of specific tyrosine residues of cytochrome C is associated with caspase-cascade inactivation. Biol Pharm Bull 30:15–20PubMedGoogle Scholar
  327. 327.
    Rodriguez-Roldan V, Garcia-Heredia JM, Navarro JA et al (2008) Effect of nitration on the physicochemical and kinetic features of wild-type and monotyrosine mutants of human respiratory cytochrome c. Biochemistry 47:12371–12379PubMedGoogle Scholar
  328. 328.
    Souza JM, Peluffo G, Radi R (2008) Protein tyrosine nitration–functional alteration or just a biomarker? Free Radic Biol Med 45:357–366PubMedGoogle Scholar
  329. 329.
    Ueta E, Kamatani T, Yamamoto T, Osaki T (2003) Tyrosine-nitration of caspase 3 and cytochrome c does not suppress apoptosis induction in squamous cell carcinoma cells. Int J Cancer 103:717–722PubMedGoogle Scholar
  330. 330.
    Diaz-Moreno I, Garcia-Heredia JM, Diaz-Quintana A et al (2011) Nitration of tyrosines 46 and 48 induces the specific degradation of cytochrome c upon change of the heme iron state to high-spin. Biochim Biophys Acta 1807:1616–1623PubMedGoogle Scholar
  331. 331.
    Castro L, Eiserich JP, Sweeney S et al (2004) Cytochrome c: a catalyst and target of nitrite-hydrogen peroxide-dependent protein nitration. Arch Biochem Biophys 421:99–107PubMedGoogle Scholar
  332. 332.
    Chen YR, Chen CL, Chen W et al (2004) Formation of protein tyrosine ortho-semiquinone radical and nitrotyrosine from cytochrome c-derived tyrosyl radical. J Biol Chem 279:18054–18062PubMedGoogle Scholar
  333. 333.
    Basova LV, Kurnikov IV, Wang L et al (2007) Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and turning on the peroxidase activity. Biochemistry 46:3423–3434PubMedCentralPubMedGoogle Scholar
  334. 334.
    Nakagawa D, Ohshima Y, Takusagawa M et al (2001) Functional modification of cytochrome c by peroxynitrite in an electron transfer reaction. Chem Pharm Bull (Tokyo) 49:1547–1554Google Scholar
  335. 335.
    Florence TM (1985) The degradation of cytochrome c by hydrogen peroxide. J Inorg Biochem 23:131–141PubMedGoogle Scholar
  336. 336.
    Radi R, Thomson L, Rubbo H, Prodanov E (1991) Cytochrome c-catalyzed oxidation of organic molecules by hydrogen peroxide. Arch Biochem Biophys 288:112–117PubMedGoogle Scholar
  337. 337.
    Chen YR, Deterding LJ, Sturgeon BE et al (2002) Protein oxidation of cytochrome C by reactive halogen species enhances its peroxidase activity. J Biol Chem 277:29781–29791PubMedGoogle Scholar
  338. 338.
    Kagan VE, Bayir HA, Belikova NA et al (2009) Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med 46:1439–1453PubMedCentralPubMedGoogle Scholar
  339. 339.
    Oursler MJ, Bradley EW, Elfering SL, Giulivi C (2005) Native, not nitrated, cytochrome c and mitochondria-derived hydrogen peroxide drive osteoclast apoptosis. Am J Physiol Cell Physiol 288:C156–C168PubMedGoogle Scholar
  340. 340.
    Abriata LA, Cassina A, Tortora V et al (2009) Nitration of solvent-exposed tyrosine 74 on cytochrome c triggers heme iron-methionine 80 bond disruption. Nuclear magnetic resonance and optical spectroscopy studies. J Biol Chem 284:17–26PubMedGoogle Scholar
  341. 341.
    Giulivi C, Poderoso JJ, Boveris A (1998) Production of nitric oxide by mitochondria. J Biol Chem 273:11038–11043PubMedGoogle Scholar
  342. 342.
    Radi R, Cassina A, Hodara R et al (2002) Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451–1464PubMedGoogle Scholar
  343. 343.
    Kim SC, Sprung R, Chen Y et al (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23:607–618PubMedGoogle Scholar
  344. 344.
    Azzi A, Montecucco C, Richter C (1975) The use of acetylated ferricytochrome c for the detection of superoxide radicals produced in biological membranes. Biochem Biophys Res Commun 65:597–603Google Scholar
  345. 345.
    Arnesen T (2011) Towards a functional understanding of protein N-terminal acetylation. PLoS Biol 9:e1001074PubMedCentralPubMedGoogle Scholar
  346. 346.
    Polevoda B, Norbeck J, Takakura H et al (1999) Identification and specificities of N-terminal acetyltransferases from Saccharomyces cerevisiae. EMBO J 18:6155–6168PubMedGoogle Scholar
  347. 347.
    Polevoda B, Sherman F (2000) Nalpha -terminal acetylation of eukaryotic proteins. J Biol Chem 275:36479–36482PubMedGoogle Scholar
  348. 348.
    Hershko A, Heller H, Eytan E et al (1984) Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown. Proc Natl Acad Sci USA 81:7021–7025PubMedGoogle Scholar
  349. 349.
    Matsuura S, Arpin M, Hannum C et al (1981) In vitro synthesis and posttranslational uptake of cytochrome c into isolated mitochondria: role of a specific addressing signal in the apocytochrome. Proc Natl Acad Sci USA 78:4368–4372PubMedGoogle Scholar
  350. 350.
    Laz TM, Pietras DF, Sherman F (1984) Differential regulation of the duplicated isocytochrome c genes in yeast. Proc Natl Acad Sci USA 81:4475–4479PubMedGoogle Scholar
  351. 351.
    Prezant T, Pfeifer K, Guarente L (1987) Organization of the regulatory region of the yeast CYC7 gene: multiple factors are involved in regulation. Mol Cell Biol 7:3252–3259PubMedCentralPubMedGoogle Scholar
  352. 352.
    Zhang Z, Gerstein M (2003) The human genome has 49 cytochrome c pseudogenes, including a relic of a primordial gene that still functions in mouse. Gene 312:61–72PubMedGoogle Scholar
  353. 353.
    Limbach KJ, Wu R (1985) Characterization of two Drosophila melanogaster cytochrome c genes and their transcripts. Nucleic Acids Res 13:631–644PubMedCentralPubMedGoogle Scholar
  354. 354.
    Swanson MS, Zieminn SM, Miller DD et al (1985) Developmental expression of nuclear genes that encode mitochondrial proteins: insect cytochromes c. Proc Natl Acad Sci USA 82:1964–1968PubMedGoogle Scholar
  355. 355.
    Kim IC, Nolla H (1986) Antigenic analysis of testicular cytochromes c using monoclonal antibodies. Biochem Cell Biol 64:1211–1217PubMedGoogle Scholar
  356. 356.
    Kim IC, Sabourin CL (1986) Antigenic and size differences between somatic and testicular cytochromes c. Biochem Biophys Res Commun 141:131–136PubMedGoogle Scholar
  357. 357.
    Scarpulla RC, Agne KM, Wu R (1981) Isolation and structure of a rat cytochrome c gene. J Biol Chem 256:6480–6486PubMedGoogle Scholar
  358. 358.
    Scarpulla RC (1984) Processed pseudogenes for rat cytochrome c are preferentially derived from one of three alternate mRNAs. Mol Cell Biol 4:2279–2288PubMedCentralPubMedGoogle Scholar
  359. 359.
    Huttemann M, Jaradat S, Grossman LI (2003) Cytochrome c oxidase of mammals contains a testes-specific isoform of subunit VIb–the counterpart to testes-specific cytochrome c? Mol Reprod Dev 66:8–16PubMedGoogle Scholar
  360. 360.
    Narisawa S, Hecht NB, Goldberg E et al (2002) Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy. Mol Cell Biol 22:5554–5562PubMedCentralPubMedGoogle Scholar
  361. 361.
    Virbasius JV, Scarpulla RC (1988) Structure and expression of rodent genes encoding the testis-specific cytochrome c. Differences in gene structure and evolution between somatic and testicular variants. J Biol Chem 263:6791–6796PubMedGoogle Scholar
  362. 362.
    Hennig B (1975) Change of cytochrome c structure during development of the mouse. Eur J Biochem 55:167–183PubMedGoogle Scholar
  363. 363.
    Davies AM, Guillemette JG, Smith M et al (1993) Redesign of the interior hydrophilic region of mitochondrial cytochrome c by site-directed mutagenesis. Biochemistry 32:5431–5435PubMedGoogle Scholar
  364. 364.
    Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230PubMedGoogle Scholar
  365. 365.
    Han D, Williams E, Cadenas E (2001) Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem J 353:411–416PubMedGoogle Scholar
  366. 366.
    Han D, Canali R, Rettori D, Kaplowitz N (2003) Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. Mol Pharmacol 64:1136–1144PubMedGoogle Scholar
  367. 367.
    Kadenbach B, Arnold S, Lee I, Huttemann M (2004) The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases. Biochim Biophys Acta 1655:400–408PubMedGoogle Scholar
  368. 368.
    Turrens JF, Alexandre A, Lehninger AL (1985) Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch Biochem Biophys 237:408–414PubMedGoogle Scholar
  369. 369.
    Aoki H, Kang PM, Hampe J et al (2002) Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes. J Biol Chem 277:10244–10250PubMedGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Sobia Zaidi
    • 1
  • Md. Imtaiyaz Hassan
    • 1
  • Asimul Islam
    • 1
  • Faizan Ahmad
    • 1
  1. 1.Centre for Interdisciplinary Research in Basic SciencesJamia Millia IslamiaNew DelhiIndia

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