Molecular and Cellular Biochemistry

, Volume 138, Issue 1–2, pp 177–181 | Cite as

Common structure of the catalytic sites of mammalian and bacterial toxin ADP-ribosyltransferases

  • Ian J. Okazaki
  • Joel Moss
Part IV: Toxin Mono-ADP-ribosylation

Abstract

The amino acid sequences of several bacterial toxin ADP-ribosyltransferases, rabbit skeletal muscle transferases, and RT6.2, a rat T-cell NAD glycohydrolase, contain three separate regions of similarity, which can be aligned. Region I contains a critical histidine or arginine residue, region II, a group of closely spaced aromatic amino acids, and region III, an active-site glutamate which is at times seen as part of an acidic amino acid-rich sequence. In some of the bacterial ADP-ribosyltransferases, the nicotinamide moiety of NAD has been photo-crosslinked to this glutamate, consistent with its position in the active site. The similarities within these three regions, despite an absence of overall sequence similarity among the several transferases, are consistent with a common structure involved in NAD binding and ADP-ribose transfer.

Key words

ADP-ribosyltransferase diphtheria toxin cholera toxin pertussis toxin C3 exoenzyme 

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References

  1. 1.
    Moss J, Vaughan M: ADP-ribosylation of guanyl nucleotide-binding proteins by bacterial toxins. Adv Enzymol 61:303–379, 1988PubMedGoogle Scholar
  2. 2.
    Collier JR: Diphtheria toxin: Structure and function of a cytocidal protein. In: J. Moss and M. Vaughan (eds). ADP-ribosylating toxins and G Proteins. Insights into signal transduction. American Society for Microbiology, Washington, DC, 1990, pp 3–19Google Scholar
  3. 3.
    Iglewski BH: Pseudomonas toxins. In: C. Hardegree, A.T. Tu (eds.). Handbook of natural toxins. Vol. 4. Bacterial toxins. Marcel Dekker, Inc, New York, NY, 1988, pp 249–265Google Scholar
  4. 4.
    Moss J, Vaughan M: Cholera toxin andE. coli enterotoxins and their mechanisms of action. In: C. Hardegree, A.T. Tu (eds). Handbook of natural toxins. Vol 4. Bacterial toxins. Marcel Dekker, Inc, New York, NY, 1988, pp 39–87Google Scholar
  5. 5.
    Ui M: Pertussis toxin as a valuable probe for G-protein involvement signal transduction. In: J. Moss and M. Vaughan (eds). ADP-ribosylating toxins and G proteins. Insights into signal transduction. American Society for Microbiology, Washington, DC, 1990, pp 45–77Google Scholar
  6. 6.
    Lowery RG, Ludden PW: Endogenous ADP-ribosylation in procaryotes. In: J. Moss and M. Vaughan (eds). ADP-ribosylating toxins and G proteins. Insights into signal transduction. American Society for Microbiology, Washington, DC, 1990, pp 459–477Google Scholar
  7. 7.
    Aktories K, Braun U, Habermann B, Rosener S: Botulinum ADP-ribosyltransferase C3. In: J. Moss and M. Vaughan (eds). American Society for Microbiology, Washington, DC, 1990, pp 97–115Google Scholar
  8. 8.
    Just I, Mohr C, Schallehn G, Menard L, Didsbury JR, Vandekerckhove J, van Damme J, Aktories K: Purification and characterization of an ADP-ribosyltransferase produced byClostridium limosum. J Biol Chem 267: 10274–10280, 1992PubMedGoogle Scholar
  9. 9.
    Narumiya S, Sekine A, Fujiwara M: Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putativerho gene product. J Biol Chem 263:17255–17257, 1988PubMedGoogle Scholar
  10. 10.
    Sekine A, Fujiwara M, Narumiya S: Asparagine residue in therho gene product is the modification site for botulinum ADP-ribosyltransferase. J Biol Chem 266:19312–19319, 1991PubMedGoogle Scholar
  11. 11.
    Peterson JE, Larew JS-A, Graves DJ: Purification and characterization of arginine-specific ADP-ribosyltransferase from skeletal muscle microsomal membranes. J Biol Chem 265:17062–17069, 1990PubMedGoogle Scholar
  12. 12.
    Zolkiewska A, Nightingale MS, Moss J: Molecular characterization of NAD: arginine ADP-ribosyltransferase from rabbit skeletal muscle. Proc Natl Acad Sci USA 89:11352–11356, 1992PubMedGoogle Scholar
  13. 13.
    Okazaki IJ, Zolkiewska A, Nightingale MS, Moss J: Immunological and molecular conservation of mammalian glycosylphosphatidylinositol-linked ADP-ribosyltransferase from skeletal muscle. FASEB J 7:A1042, 1993Google Scholar
  14. 14.
    Takada T, Iida K, Moss J: Expression of NAD glycohydrolase activity by rat mammary adenocarcinoma cells transformed with rat T-cell alloantigen RT6.2. J Biol Chem 269:9420–9426, 1994PubMedGoogle Scholar
  15. 15.
    Koch F, Haag F, Thiele H-G: Nucleotide and deduced amino acid sequence for the mouse homologue of the rat T-cell differentiation marker RT6.2. Nucl Acids Res 18:3636, 1990PubMedGoogle Scholar
  16. 16.
    Koch F, Kashan A, Thiele H-G: The rat T-cell differentiation marker RT6.1 is more polymorphic than its alloantigenic counterpart RT6.2. Immunology 65:259–265, 1988PubMedGoogle Scholar
  17. 17.
    Koch F, Haag F, Kashan A, Thiele H-G: Primary structure of rat RT6.2. a nonglycosylated phosphatidylinositol-linked surface marker of postthymic T cells. Proc Natl Acad Sci USA 87:964–967, 1990PubMedGoogle Scholar
  18. 18.
    Thiele H-G, Koch F, Hamann A, Arndt R: Biochemical characterization of the T-cell alloantigen RT6.2. Immunology 59:195–201, 1986PubMedGoogle Scholar
  19. 19.
    Koch F, Thiele H-G, Low M: Release of the rat T cell alloantigen RT6.2 from cell membranes by phosphatidylinositol-specific phospholipase C. J Exp Med 164:1338, 1986PubMedGoogle Scholar
  20. 20.
    Rappuoli R, Pizza M: Structure and evolutionary aspects of ADH-ribosylating toxins. In: J.E. Alouf and J.H. Freer (eds) Sourcebook of bacterial protein toxins. Academic Press Inc, San Diego, CA 1991, pp. 1–21Google Scholar
  21. 21.
    Papini E, Schiavo G, Sandona D, Rappuoli R, Montecucco C: Histidine 21 is at the NAD+ binding site of diphtheria toxin. J Biol Chem 264: 12385–12388, 1989PubMedGoogle Scholar
  22. 22.
    Wozniak DJ, Hsu L-Y, Galloway DR: His-426 of thePseudomonas aeruginosa exotoxin A is required for ADP-ribosylation of elongation factor II. Proc Natl Acad Sci USA 85:8880–8884, 1988PubMedGoogle Scholar
  23. 23.
    Allured VS, Collier JR, Carroll SF, McKay DB: Structure of exotoxin A ofPseudomonas aeruginosa at 3.0 Angstrom resolution. Proc Natl Acad Sci USA 83:1320–1324, 1986PubMedGoogle Scholar
  24. 24.
    Carroll SF, Collier RJ: Amino acid sequence homology between the enzymic domain of diphtheria toxin andPseudomonas aeruginasa exotoxin A. Molec Microbiol 2:293–296, 1988Google Scholar
  25. 25.
    Domenighini M, Magagnoli C, Pizza M, Rappuoli R: Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins Molec Microbiol, in pressGoogle Scholar
  26. 26.
    Kaslow HR, Schlotterbeck JD, Mar VL, Burnette WN: Alkylation of cysteine 41, but not cysteine 200, decreases the ADP-ribosyltransferase activity of the S1 subunit of pertussis toxin. J Biol Chem 264:6386–6390 1989PubMedGoogle Scholar
  27. 27.
    Sixma TK, Pronk SE, Kalk KH, Wartna ES, van Zanten BAM, Witholt B, Hol HGJ: Crystal structure of a cholera toxin-related heat-labile enterotoxin fromE. coli. Nature 351:371–377,1991PubMedGoogle Scholar
  28. 28.
    Brandhuber BJ, Allured VS, Falbel TG, McKay DB: Mapping the enzymatic active site ofPseudomonas aeruginosa exotoxin A Proteins 3:146–154, 1988PubMedGoogle Scholar
  29. 29.
    Carroll SF, McCloskey JA, Crain PF, Oppenheimer NJ, Marschner TM, Collier JR: Photoaffinity labeling of diphtheria toxin fragmentA with NAD: Structure of the photoproduct at position 148. Proc Natl Acad Sci USA 82: 7237–7241, 1985PubMedGoogle Scholar
  30. 30.
    Carroll SF, Collier JR: NAD binding site of diphtheria toxin: Identification of a residue within the nicotinamide subsite by photochemical modification with NAD. Proc Natl Acad Sci USA 81:3307–3311, 1984PubMedGoogle Scholar
  31. 31.
    Barbieri JT, Mende-Meuller LM, Rappuoli R, Collier JR: Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD. Infect Immun 57:3549–3554, 1989PubMedGoogle Scholar
  32. 32.
    Jung M, Just I, van Damme J Vandekerckhove J, Aktories K: NAD-binding site of the C3-like ADP-ribosyltransferase fromClostridium limosum. J Biol Chem 268:23215–23218, 1993PubMedGoogle Scholar
  33. 33.
    Tweten RK, Barbieri JT, Collier RJ: Diphtheria toxin: effect of substituting sapartic acid for glutamic acid-148 on ADP-ribosyltransferase activity. J Biol Chem 260:10392–10394, 1985PubMedGoogle Scholar
  34. 34.
    Douglas CM, Collier RJ: Exotoxin A ofPseudomonas aeruginosa: substitution of glutamic acid-553 with aspartic acid drastically reduces toxicity and enzymic activity. Infect Immun 169:4967–4971, 1987Google Scholar
  35. 35.
    Pizza M, Bartoloni A, Prugnola A, Silvestri S, Rappuoli R: Subunit S1 of pertussis toxin: Mapping of the regions essential for ADP-ribosyltransferase activity. Proc Natl Acad Sci USA 85:7521–7525, 1988PubMedGoogle Scholar
  36. 36.
    Tsuji T, Inoue T, Miyama A, Okamoto K, Honda T, Miwatani T: A single amino acid substitution in the A subunit ofEscherichia coli enterotoxin results in a loss of its toxic activity. J Biol Chem 265:22520–22525 1990PubMedGoogle Scholar
  37. 37.
    Moss J, Stanley SJ, Vaughan M, Tsuji T: Interaction of ADP-ribosylation factor withEscherichia coli enterotoxin that contains an inactivating lysine 112 substitution. J Biol Chem 268:6383–6387, 1993PubMedGoogle Scholar
  38. 38.
    Harford S, Dykes CW, Hobden AN, Read MJ, Halliday IJ: Inactivation of theEscherichia coli heat-labile enterotoxin byin vitro mutagenesis of the A subunit gene. Eur J Biochem 183:311–316, 1989PubMedGoogle Scholar
  39. 39.
    Dallas WS, Falkow S: Amino acid sequence homology between cholera toxin andEschericia coli heat-labile toxin. Nature 288:499–501, 1987Google Scholar
  40. 40.
    Yamamoto T, Gojobori T, Yokota T: Evolutionary origin of pathogenic determinants in enterotoxigenicEscherichia coli andVibrio cholerae O1. J Bacteriol 169:1352–1357, 1987PubMedGoogle Scholar
  41. 41.
    Howard M, Grimaldi JC, Bazan JF, Lund FE, Santos-Argumedo L, Parkhouse RME, Walseth TF, Lee HC: Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science 262: 1056–1059, 1993PubMedGoogle Scholar
  42. 42.
    Zocchi E, Franco L, Guida L, Benatti U, Bargellesi A, Malavasi F, Lee HC, De Flora A: A single protein immunologically identified as CD38 displays NAD+ glycohydrolase, ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities at the outer surface of human erythrocytes. Biochem Biophys Res Commun 196:1459–1465, 1993PubMedGoogle Scholar
  43. 43.
    Ueda K: Poly(ADP-ribose) Synthetase. In: J. Moss and M. Vaughan (eds). ADP-ribosylating toxins and G proteins Insights into signal transduction. American Society for Microbiology, Washington, DC, 1990, pp 525–542Google Scholar
  44. 44.
    Simonin F, Poch O, Delarue M, de Murcia G: Identification of potential active-site residues in the human poly(ADP-ribose) polymerase. J Biol Chem 268:8529–8535, 1993PubMedGoogle Scholar
  45. 45.
    Marsischky GT, Ikejima M, Suzuki H, Sugimura T, Esumi H, Miwa M, Collier RJ: Directed mutagenesis of glutamic acid 988 of poly(ADP-ricose) polymerase. In: G.G. Poirier, P. Moreau (eds) ADP-ribosylation reactions. Springer-Verlag, New York, NY, 1992, pp 47–52Google Scholar
  46. 46.
    Jackson DG, Bell JI: Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. J Immunol 144: 2811–2815, 1990PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Ian J. Okazaki
    • 1
  • Joel Moss
    • 1
  1. 1.Laboratory of Cellular Metabolism, National Heart, Lung and Blood InstituteNational Institutes of HealthBethesdaUSA

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