The diphthamide modification pathway from Saccharomyces cerevisiae - revisited

Molecular Microbiology

Volumn 94, Issue 6, 2014, Pages 1213-1226

  Schaffrath, Raffael ^a,b   Abdel Fattah, Wael ^b   Klassen, Roland ^b   Stark, Michael J R ^c  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b UNIVERSITY OF KASSEL   (Germany)

^c UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DIPHTHAMIDE; ELONGATION FACTOR; ELONGATION FACTOR 2; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; UNCLASSIFIED DRUG; HISTIDINE; SACCHAROMYCES CEREVISIAE PROTEIN;

ADENOSINE DIPHOSPHATE RIBOSYLATION; AMIDATION; CELL PROLIFERATION; DEMETHYLATION; DPH1 GENE; DPH5 GENE; DPH6 GENE; DPH7 GENE; FUNGAL GENE; FUNGUS GROWTH; GENE INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ACETYLATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN METHYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN SYNTHESIS; PROTEIN TARGETING; REVIEW; RNA SYNTHESIS; RNA TRANSLATION; RNA TRANSPORT; SACCHAROMYCES CEREVISIAE; UBIQUITINATION; ANALOGS AND DERIVATIVES; CHEMISTRY; GENETICS; METABOLISM; MOLECULAR EVOLUTION;

SACCHAROMYCES CEREVISIAE;

EVOLUTION, MOLECULAR; HISTIDINE; PEPTIDE ELONGATION FACTOR 2; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 84915811228     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/mmi.12845     Document Type: Review

References (109)

1. Abdel-Fattah, W., Scheidt, V., Uthman, S., Stark, M.J., and Schaffrath, R. (2013) Insights into diphthamide, key diphtheria toxin effector. Toxins 5: 958-968.
2. Andersen, G.R., Nissen, P., and Nyborg, J. (2003) Elongation factors in protein biosynthesis. Trends Biochem Sci 28: 434-441.
3. Andriole, V.T. (1999) The 1998 Garrod lecture. Current and future antifungal therapy: new targets for antifungal agents. J Antimicrob Chemother 44: 151-162.
4. Argüelles, S., Camandola, S., Hutchison, E.R., Cutler, R.G., Ayala, A., and Mattson, M.P. (2013) Molecular control of the amount, subcellular location, and activity state of translation elongation factor 2 in neurons experiencing stress. Free Radic Biol Med 61: 61-71.
5. Argüelles, S., Camandola, S., Cutler, R.G., Ayala, A., and Mattson, M.P. (2014) Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions. Free Radic Biol Med 67: 131-138.
6. Bär, C., Zabel, R., Liu, S., Stark, M.J., and Schaffrath, R. (2008) A versatile partner of eukaryotic protein complexes that is involved in multiple biological processes: Kti11/Dph3. Mol Microbiol 69: 1221-1233.
7. Bektaş, M., Nurten, R., Ergen, K., and Bermek, E. (2006) Endogenous ADP-ribosylation for eukaryotic elongation factor 2: evidence of two different sites and reactions. Cell Biochem Funct 24: 369-380.
8. Botet, J., Rodriguez-Mateos, M., Ballesta, J.P., Revuelta, J.L., and Remacha, M. (2008) A chemical genomic screen in Saccharomyces cerevisiae reveals a role for diphthamidation of translation elongation factor 2 in inhibition of protein synthesis by sordarin. Antimicrob Agents Chemother 52: 1623-1629.
9. Burman, J.D., Stevenson, C.E., Sawers, R.G., and Lawson, D.M. (2007) The crystal structure of Escherichia coli TdcF, a member of the highly conserved YjgF/YER057c/UK114 family. BMC Struct Biol 7: 30.
10. Butler, A.R., White, J.H., Folawiyo, Y., Edlin, A., Gardiner, D., and Stark, M.J. (1994) Two Saccharomyces cerevisiae genes which control sensitivity to G1 arrest induced by Kluyveromyces lactis toxin. Mol Cell Biol 14: 6306-6316.
11. Carette, J.E., Guimaraes, C.P., Varadarajan, M., Park, A.S., Wuethrich, I., Godarova, A., etal. (2009) Haploid genetic screens in human cells identify host factors used by pathogens. Science 326: 1231-1235.
12. Chen, C.M., and Behringer, R.R. (2004) Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis. Genes Dev 18: 320-332.
13. Chen, C.M., and Behringer, R.R. (2005) OVCA1: tumor suppressor gene. Curr Opin Genet Dev 15: 49-54.
14. Chen, J.Y., and Bodley, J.W. (1988) Biosynthesis of diphthamide in Saccharomyces cerevisiae. Partial purification and characterization of a specific S-adenosylmethionine: elongation factor 2 methyltransferase. J Biol Chem 263: 11692-11696.
15. Chen, J.Y., Bodley, J.W., and Livingston, D.M. (1985) Diphtheria toxin-resistant mutants of Saccharomyces cerevisiae. Mol Cell Biol 5: 3357-3360.
16. Chen, Z., Zhang, H., Jablonowski, D., Zhou, X., Ren, X., Hong, X., etal. (2006) Mutations in ABO1/ELO2, one subunit of holo-Elongator, increase ABA sensitivity and drought tolerance in Arabidopsis. Mol Cell Biol 26: 6902-6912.
17. Collier, R.J. (1975) Diphtheria toxin: mode of action and structure. Bacteriol Rev 39: 54-85.
18. Collins, S.R., Kemmeren, P., Zhao, X.C., Greenblatt, J.F., Spencer, F., Holstege, F.C., etal. (2007) Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae. Mol Cell Proteomics 6: 439-450.
19. Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E.D., Sevier, C.S., etal. (2010) The genetic landscape of a cell. Science 327: 425-431.
20. de Crécy-Lagard, V., Forouhar, F., Brochier-Armanet, C., Tong, L., and Hunt, J.F. (2012) Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage. Biol Direct 7: 32.
21. Czworkowski, J., Wang, J., Steitz, T.A., and Moore, P.B. (1994) The crystal structure of elongation factor G complexed with GDP, at 2.7 A resolution. EMBO J 13: 3661-3668.
22. Deng, Q., and Barbieri, J.T. (2008) Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins. Annu Rev Microbiol 62: 271-288.
23. Domínguez, J.M., and Martín, J.J. (1998) Identification of elongation factor 2 as the essential protein targeted by sordarins in Candida albicans. Antimicrob Agents Chemother 42: 2279-2283.
24. Domínguez, J.M., Gómez-Lorenzo, M.G., and Martín, J.J. (1999) Sordarin inhibits fungal protein synthesis by blocking translocation differently to fusidic acid. J Biol Chem 274: 22423-22427.
25. Dong, M., Su, X., Dzikovski, B., Dando, E.E., Zhu, X., Du, J., etal. (2014) Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryotic diphthamide biosynthesis. J Am Chem Soc 136: 1754-1757.
26. Dunlop, P.C., and Bodley, J.W. (1983) Biosynthetic labeling of diphthamide in Saccharomyces cerevisiae. J Biol Chem 258: 4754-4758.
27. Fendrick, J.L., and Iglewski, W.J. (1989) Endogenous ADP-ribosylation of elongation factor 2 in polyoma virus-transformed baby hamster kidney cells. Proc Natl Acad Sci USA 86: 554-557.
28. Fendrick, J.L., Iglewski, W.J., Moehring, J.M., and Moehring, T.J. (1992) Characterization of the endogenous ADP-ribosylation of wild-type and mutant elongation factor 2 in eukaryotic cells. Eur J Biochem 205: 25-31.
29. Fichtner, L., and Schaffrath, R. (2002) KTI11 and KTI13, Saccharomyces cerevisiae genes controlling sensitivity to G1 arrest induced by Kluyveromyces lactis zymocin. Mol Microbiol 44: 865-875.
30. Fichtner, L., Jablonowski, D., Schierhorn, A., Kitamoto, H.K., Stark, M.J., and Schaffrath, R. (2003) Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification. Mol Microbiol 49: 1297-1307.
31. Greenwood, C., Selth, L.A., Dirac-Svejstrup, A.B., and Svejstrup, J.Q. (2009) An iron-sulfur cluster domain in Elp3 important for the structural integrity of elongator. J Biol Chem 284: 141-149.
32. Greganova, E., Altmann, M., and Bütikofer, P. (2011) Unique modifications of translation elongation factors. FEBS J 278: 2613-2624.
33. Gupta, P.K., Liu, S., Batavia, M.P., and Leppla, S.H. (2008) The diphthamide modification on elongation factor-2 renders mammalian cells resistant to ricin. Cell Microbiol 10: 1687-1694.
34. Honjo, T., Nishizuka, Y., and Hayaishi, O. (1968) Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J Biol Chem 243: 3553-3555.
35. Hontz, R.D., Niederer, R.O., Johnson, J.M., and Smith, J.S. (2009) Genetic identification of factors that modulate ribosomal DNA transcription in Saccharomyces cerevisiae. Genetics 182: 105-119.
36. Huang, B., Johansson, M.J., and Byström, A.S. (2005) An early step in wobble uridine tRNA modification requires the Elongator complex. RNA 11: 424-436.
37. Huang, B., Lu, J., and Byström, A.S. (2008) A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae. RNA 14: 2183-2194.
38. Iglewski, B.H., Liu, P.V., and Kabat, D. (1977) Mechanism of action of Pseudomonas aeruginosa exotoxin adenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo. Infect Immun 15: 138-144.
39. Iglewski, W.J. (1994) Cellular ADP-ribosylation of elongation factor 2. Mol Cell Biochem 138: 131-133.
40. Iglewski, W.J., Lee, H., and Muller, P. (1984) ADP-ribosyltransferase from beef liver which ADP-ribosylates elongation factor-2. FEBS Lett 173: 113-118.
41. Jablonowski, D., and Schaffrath, R. (2007) Zymocin, a composite chitinase and tRNase killer toxin from yeast. Biochem Soc Trans 35: 1533-1537.
42. Jäger, D., Werdan, K., and Müller-Werdan, U. (2011) Endogenous ADP-ribosylation of elongation factor-2 by interleukin-1β. Mol Cell Biochem 348: 125-128.
43. Jørgensen, R., Ortiz, P.A., Carr-Schmid, A., Nissen, P., Kinzy, T.G., and Andersen, G.R. (2003) Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase. Nat Struct Biol 10: 379-385.
44. Jørgensen, R., Yates, S.P., Teal, D.J., Nilsson, J., Prentice, G.A., Merrill, A.R., and Andersen, G.R. (2004) Crystal structure of ADP-ribosylated ribosomal translocase from Saccharomyces cerevisiae. J Biol Chem 279: 45919-45925.
45. Jørgensen, R., Merrill, A.R., and Andersen, G.R. (2006) The life and death of translation elongation factor 2. Biochem Soc Trans 34: 1-6.
46. Jørgensen, R., Purdy, A.E., Fieldhouse, R.J., Kimber, M.S., Bartlett, D.H., and Merrill, A.R. (2008a) Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae. J Biol Chem 283: 10671-10678.
47. Jørgensen, R., Wang, Y., Visschedyk, D., and Merrill, A.R. (2008b) The nature and character of the transition state for the ADP-ribosyltransferase reaction. EMBO Rep 9: 802-809.
48. Justice, M.C., Hsu, M.J., Tse, B., Ku, T., Balkovec, J., Schmatz, D., and Nielsen, J. (1998) Elongation factor 2 as a novel target for selective inhibition of fungal protein synthesis. J Biol Chem 273: 3148-3151.
49. Kambampati, R., and Lauhon, C.T. (2003) MnmA and IscS are required for in vitro 2-thiouridine biosynthesis in Escherichia coli. Biochemistry 42: 1109-1117.
50. Kimata, Y., and Kohno, K. (1994) Elongation factor 2 mutants deficient in diphthamide formation show temperature-sensitive cell growth. J Biol Chem 269: 13497-13501.
51. Krogan, N.J., Cagney, G., Yu, H., Zhong, G., Guo, X., Ignatchenko, A., etal. (2006) Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 440: 637-643.
52. Lambrecht, J.A., Flynn, J.M., and Downs, D.M. (2012) Conserved YjgF protein family deaminates reactive enamine/imine intermediates of pyridoxal 5′-phosphate (PLP)-dependent enzyme reactions. J Biol Chem 287: 3454-3461.
53. Lee, H., and Iglewski, W.J. (1984) Cellular ADP-ribosyltransferase with the same mechanism of action as diphtheria toxin and Pseudomonas toxin A. Proc Natl Acad Sci USA 81: 2703-2707.
54. Lee, I., Li, Z., and Marcotte, E.M. (2007) An improved, bias-reduced probabilistic functional gene network of baker's yeast, Saccharomyces cerevisiae. PLoS ONE 2: e988.
55. Lin, H. (2011) S-Adenosylmethionine-dependent alkylation reactions: when are radical reactions used? Bioorg Chem 39: 161-170.
56. Lin, Z., Su, X., Chen, W., Ci, B., Zhang, S., and Lin, H. (2014) Dph7 catalyzes a previously unknown demethylation step in diphthamide biosynthesis. J Am Chem Soc 136: 6179-6182.
57. Liu, S., and Leppla, S.H. (2003) Retroviral insertional mutagenesis identifies a small protein required for synthesis of diphthamide, the target of bacterial ADP-ribosylating toxins. Mol Cell 12: 603-613.
58. Liu, S., Milne, G.T., Kuremsky, J.G., Fink, G.R., and Leppla, S.H. (2004) Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. Mol Cell Biol 24: 9487-9497.
59. Liu, S., Wiggins, J.F., Sreenath, T., Kulkarni, A.B., Ward, J.M., and Leppla, S.H. (2006) Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development. Mol Cell Biol 26: 3835-3841.
60. Liu, S., Bachran, C., Gupta, P., Miller-Randolph, S., Wang, H., Crown, D., etal. (2012) Diphthamide modification on eukaryotic elongation factor 2 is needed to assure fidelity of mRNA translation and mouse development. Proc Natl Acad Sci USA 109: 13817-13822.
61. Mateyak, M.K., and Kinzy, T.G. (2013) ADP-ribosylation of translation elongation factor 2 by diphtheria toxin in yeast inhibits translation and cell separation. J Biol Chem 288: 24647-24655.
62. Mattheakis, L.C., Shen, W.H., and Collier, R.J. (1992) DPH5, a methyltransferase gene required for diphthamide biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol 12: 4026-4037.
63. Mehlgarten, C., Jablonowski, D., Wrackmeyer, U., Tschitschmann, S., Sondermann, D., Jäger, G., etal. (2010) Elongator function in tRNA wobble uridine modification is conserved between yeast and plants. Mol Microbiol 75: 1082-1094.
64. Moehring, J.M., Moehring, T.J., and Danley, D.E. (1980) Posttranslational modification of elongation factor 2 in diphtheria-toxin-resistant mutants of CHO-K1 cells. Proc Natl Acad Sci USA 77: 1010-1014.
65. Moehring, T.J., Danley, D.E., and Moehring, J.M. (1984) In vitro biosynthesis of diphthamide, studied with mutant Chinese hamster ovary cells resistant to diphtheria toxin. Mol Cell Biol 4: 642-650.
66. Nakanishi, K., Fukai, S., Ikeuchi, Y., Soma, A., Sekine, Y., and Nureki, O. (2005) Structural basis for lysidine formation by ATP pyrophosphatase accompanied by a lysine-specific loop and a tRNA-recognition domain. Proc Natl Acad Sci USA 102: 7487-7492.
67. Nilsson, J., and Nissen, P. (2005) Elongation factors on the ribosome. Curr Opin Struct Biol 15: 349-354.
68. Nissen, P., Kjeldgaard, M., Thirup, S., Polekhina, G., Reshetnikova, L., Clark, B.F., and Nyborg, J. (1995) Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog. Science 270: 1464-1472.
69. Nobukuni, Y., Kohno, K., and Miyagawa, K. (2005) Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphthamide on elongation factor 2. J Biol Chem 280: 10572-10577.
70. Odds, F.C., Brown, A.J., and Gow, N.A. (2003) Antifungal agents: mechanisms of action. Trends Microbiol 11: 272-279.
71. Ortiz, P.A., and Kinzy, T.G. (2005) Dominant-negative mutant phenotypes and the regulation of translation elongation factor 2 levels in yeast. Nucleic Acids Res 33: 5740-5748.
72. Ortiz, P.A., Ulloque, R., Kihara, G.K., Zheng, H., and Kinzy, T.G. (2006) Translation elongation factor 2 anticodon mimicry domain mutants affect fidelity and diphtheria toxin resistance. J Biol Chem 281: 32639-32648.
73. Pappenheimer, A.M., Jr (1977) Diphtheria toxin. Annu Rev Biochem 46: 69-94.
74. Paraskevopoulou, C., Fairhurst, S.A., Lowe, D.J., Brick, P., and Onesti, S. (2006) The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Mol Microbiol 59: 795-806.
75. Proudfoot, M., Sanders, S.A., Singer, A., Zhang, R., Brown, G., Binkowski, A., etal. (2008) Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain. J Mol Biol 375: 301-315.
76. Rezgui, V.A., Tyagi, K., Ranjan, N., Konevega, A.L., Mittelstaet, J., Rodnina, M.V., etal. (2013) tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding. Proc Natl Acad Sci USA 110: 12289-12294.
77. Rodnina, M.V., Savelsbergh, A., Katunin, V.I., and Wintermeyer, W. (1997) Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome. Nature 385: 37-41.
78. Roy, V., Ghani, K., and Caruso, M. (2010) A dominant-negative approach that prevents diphthamide formation confers resistance to Pseudomonas exotoxin A and diphtheria toxin. PLoS ONE 5: e15753.
79. Sahi, C., and Craig, E.A. (2007) Network of general and specialty J protein chaperones of the yeast cytosol. Proc Natl Acad Sci USA 104: 7163-7168.
80. Sayhan, O., Ozdemirli, M., Nurten, R., and Bermek, E. (1986) On the nature of cellular ADP-ribosyltransferase from rat liver specific for elongation factor 2. Biochem Biophys Res Commun 139: 1210-1214.
81. Schaffrath, R., and Stark, M.J.R. (2014) Decoding the biosynthesis and function of diphthamide, an enigmatic modification of translation elongation factor 2 (EF2). Microb Cell 1: 203-205.
82. Selvadurai, K., Wang, P., Seimetz, J., and Huang, R.H. (2014) Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism. Nat Chem Biol 10: 810-812.
83. Shastry, M., Nielsen, J., Ku, T., Hsu, M.J., Liberator, P., Anderson, J., etal. (2001) Species-specific inhibition of fungal protein synthesis by sordarin: identification of a sordarin-specificity region in eukaryotic elongation factor 2. Microbiology 147: 383-390.
84. Shi, Y., Stefan, C.J., Rue, S.M., Teis, D., and Emr, S.D. (2011) Two novel WD40 domain-containing proteins, Ere1 and Ere2, function in the retromer-mediated endosomal recycling pathway. Mol Biol Cell 22: 4093-4107.
85. Sinha, S., Rappu, P., Lange, S.C., Mäntsälä, P., Zalkin, H., and Smith, J.L. (1999) Crystal structure of Bacillus subtilis YabJ, a purine regulatory protein and member of the highly conserved YjgF family. Proc Natl Acad Sci USA 96: 13074-13079.
86. Sitikov, A.S., Davydova, E.K., and Ovchinnikov, L.P. (1984) Endogenous ADP-ribosylation of elongation factor 2 in polyribosome fraction of rabbit reticulocytes. FEBS Lett 176: 261-263.
87. Sjölinder, M., Uhlmann, J., and Ponstingl, H. (2002) DelGEF, a homologue of the Ran guanine nucleotide exchange factor RanGEF, binds to the exocyst component Sec5 and modulates secretion. FEBS Lett 532: 211-215.
88. Spahn, C.M., Gomez-Lorenzo, M.G., Grassucci, R.A., Jørgensen, R., Andersen, G.R., Beckmann, R., etal. (2004) Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome facilitate tRNA translocation. EMBO J 23: 1008-1019.
89. Su, X., Chen, W., Lee, W., Jiang, H., Zhang, S., and Lin, H. (2012a) YBR246W is required for the third step of diphthamide biosynthesis. J Am Chem Soc 134: 773-776.
90. Su, X., Lin, Z., Chen, W., Jiang, H., Zhang, S., and Lin, H. (2012b) Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. Proc Natl Acad Sci USA 109: 19983-19987.
91. Su, X., Lin, Z., and Lin, H. (2013) The biosynthesis and biological function of diphthamide. Crit Rev Biochem Mol Biol 48: 515-521.
92. Sun, J., Zhang, J., Wu, F., Xu, C., Li, S., Zhao, W., etal. (2005) Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module. Biochemistry 44: 8801-8809.
93. Taylor, D.J., Nilsson, J., Merrill, A.R., Andersen, G.R., Nissen, P., and Frank, J. (2007) Structures of modified eEF2 80S ribosome complexes reveal the role of GTP hydrolysis in translocation. EMBO J 26: 2421-2431.
94. Thakur, A., Chitoor, B., Goswami, A.V., Pareek, G., Atreya, H.S., and D'Silva, P. (2012) Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4. J Biol Chem 287: 13194-13205.
95. Uthman, S., Kheir, E., Bär, C., Jablonowski, D., and Schaffrath, R. (2011) Growth inhibition strategies based on antimicrobial microbes/toxins. In Science against Microbial Pathogens: Communicating Current Research and Technological Advances, Vol. 2. Mendez-Vilas, A. (ed.). Badajoz: Formatex Research Center, pp. 1321-1329.
96. Uthman, S., Liu, S., Giorgini, F., Stark, M.J.R., Costanzo, M., and Schaffrath, R. (2012) Diphtheria disease and genes involved in formation of diphthamide, key effector of the diphtheria toxin. In Insight and Control of Infectious Disease in Global Scenario. Roy, P.K. (ed.). Rijeka: InTech Open Access Publisher, pp. 333-356.
97. Uthman, S., Bär, C., Scheidt, V., Liu, S., ten Have, S., Giorgini, F., etal. (2013) The amidation step of diphthamide biosynthesis in yeast requires DPH6, a gene identified through mining the DPH1-DPH5 interaction network. PLoS Genet 9: e1003334.
98. Van Ness, B.G., Howard, J.B., and Bodley, J.W. (1980a) ADP-ribosylation of elongation factor 2 by diphtheria toxin. NMR spectra and proposed structures of ribosyl-diphthamide and its hydrolysis products. J Biol Chem 255: 10710-10716.
99. Van Ness, B.G., Howard, J.B., and Bodley, J.W. (1980b) ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products. J Biol Chem 255: 10717-10720.
100. Voorhees, R.M., and Ramakrishnan, V. (2013) Structural basis of the translational elongation cycle. Annu Rev Biochem 82: 203-236.
101. Webb, T.R., Cross, S.H., McKie, L., Edgar, R., Vizor, L., Harrison, J., etal. (2008) Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development. J Cell Sci 121: 3140-3145.
102. Wei, H., Bera, T.K., Wayne, A.S., Xiang, L., Colantonio, S., Chertov, O., and Pastan, I. (2013) A modified form of diphthamide causes immunotoxin resistance in a lymphoma cell line with a deletion of the WDR85 gene. J Biol Chem 288: 12305-12312.
103. Yates, S.P., Jorgensen, R., Andersen, G.R., and Merrill, A.R. (2006) Stealth and mimicry by deadly bacterial toxins. Trends Biochem Sci 31: 123-133.
104. Yu, H., Braun, P., Yildirim, M.A., Lemmens, I., Venkatesan, K., Sahalie, J., etal. (2008) High-quality binary protein interaction map of the yeast interactome network. Science 322: 104-110.
105. Yu, Y.R., You, L.R., Yan, Y.T., and Chen, C.M. (2014) Role of OVCA1/DPH1 in craniofacial abnormalities of Miller-Dieker syndrome. Hum Mol Genet 23: 5579-5596.
106. Zabel, R., Bär, C., Mehlgarten, C., and Schaffrath, R. (2008) Yeast α-tubulin suppressor Ats1/Kti13 relates to the Elongator complex and interacts with Elongator partner protein Kti11. Mol Microbiol 69: 175-187.
107. Zhang, Y., Zhu, X., Torelli, A.T., Lee, M., Dzikovski, B., Koralewski, R.M., etal. (2010) Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme. Nature 465: 891-896.
108. Zhu, X., Kim, J., Su, X., and Lin, H. (2010) Reconstitution of diphthine synthase activity in vitro. Biochemistry 49: 9649-9657.
109. Zhu, X., Dzikovski, B., Su, X., Torelli, A.T., Zhang, Y., Ealick, S.E., etal. (2011) Mechanistic understanding of Pyrococcus horikoshii Dph2, a [4Fe-4S] enzyme required for diphthamide biosynthesis. Mol Biosyst 7: 74-81.