Sequence and Structural Links between Distant ADP-Ribosyltransferase Families

  • J. Fernando Bazan
  • Friedrich Koch-Nolte
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 419)

Abstract

The low resolution structure of the Pseudomonas aeroginosa exotoxin A (ETA) presented in 1986 provided the first tantalizing three-dimensional view of an ADP-ribosyltransferase (ADPRT) catalytic domain. The major features of this protein fold have recurred in the more recently solved crystal structures of the cholera toxin-related heatlabile enterotoxin (LT), diphtheria toxin (DT) and pertussis toxin (PT). A core set of α+β elements define a minimal, conserved scaffold with remarkably plastic sequence requirements - only a single glutamic acid residue critical to catalytic activity is invariant. Other interchangeable residues in locations important for catalysis and binding are suggested by the cocrystal structures of DT with the inhibitor ApUp, ETA with bound AMP and nicotinamide, and DT with substrate NAD - in close accord with labeling and mutagenic data. Faint sequence resemblances that were earlier noticed among prokaryotic ADPRTs have now been securely extended by the structural concordance between toxin folds; more recently, eukaryotic ADPRTs have surfaced and their sequences can be reliably threaded into the conserved core fold. We will briefly summarize efforts in Palo Alto and Hamburg to explore these latter relationships, and to mount a rigorous search for new ADPRT families in the growing sequence databases.

Keywords

Catalysis Explosive Disulfide Pseudomonas Adenine 

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References

  1. 1.
    Bork, P., C. Ouzounis, C. Sander. 1994. From genome sequences to protein function. Cun: Opin. Struct. Biol. 4: 393–403.CrossRefGoogle Scholar
  2. 2.
    Pawson, T. 1995. Protein modules and signalling networks. Nature 373: 573–580.PubMedCrossRefGoogle Scholar
  3. 3.
    Koch-Nolte, F., F. Haag, R. Kastelein, J.F. Bazan. 1996. Uncovered-the family relationship of a T-cell membrane protein and bacterial toxins. Immunol. Today 17: 402–405.PubMedCrossRefGoogle Scholar
  4. 4.
    Holm, L., C. Sander. 1996. Mapping the protein universe. Science 273: 595–603.PubMedCrossRefGoogle Scholar
  5. 5.
    Fischer, D., D. Rice, J.U. Bowie, D. Eisenberg. 1996. Assigning amino acid sequences to 3-dimensional protein folds. FASEB J. 10: 126–136.PubMedGoogle Scholar
  6. 6.
    Rost, B., A. Valencia. 1996. Pitfalls of protein sequence analysis. Cun: Opin. Biotech. 7: 457–461.CrossRefGoogle Scholar
  7. 7.
    Bork, P., T. Gibson. 1996. Applying motif and profile searches. Meth. Enzym. 266: 162–184.PubMedCrossRefGoogle Scholar
  8. 8.
    Firestine, S.M., A.E. Nixon, S.J. Benkovic. 1996. Threading your way to protein function. Chem. and Biol. 3: 779–783.CrossRefGoogle Scholar
  9. 9.
    Casari, G., C. Sander, A. Valencia. 1995. A method to predict functional residues in proteins. Nature Struct. Biol. 2: 171–178.PubMedCrossRefGoogle Scholar
  10. 10.
    Lichtarge, O., H.R. Bourne, F.E. Cohen. 1996. An evolutionary trace method defines binding surfaces common to protein families. J. Moke. Biol. 257: 342–358.CrossRefGoogle Scholar
  11. 11.
    Brannigan, J.A., G. Dodson, H.J. Duggleby, P.C. Moody, J.L. Smith, D.R. Tomchick, A.G. Murzin. 1995. A protein catalytic framework with an N-terminal nucleophile is capable of self-activation. Nature 378: 416–419.PubMedCrossRefGoogle Scholar
  12. 12.
    Fauman, E.B., M.A. Saper. 1996. Structure and function of the protein tyrosine phosphatases. Trends Biochem. Sci. 27:413–417.CrossRefGoogle Scholar
  13. 13.
    Allured, V.S., R.J. Collier, S.F. Carroll, D.B. McKay. 1986. Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Å resolution. Proc. Natl. Acad. Sci. USA 83: 1320–1324.PubMedCrossRefGoogle Scholar
  14. 14.
    Sixma, T.K., S.E. Pronk, K.H. Kalk, E.S. Wartna, B.A.M. Van Zanten, B. Witholt, W.G.J. Hol. 1991. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature 351: 371–377.Google Scholar
  15. 15.
    Choe, S., M.J. Bennett, G. Fujii, P.M. Curmi, K.A. Kantardjieff, R.J. Collier, D. Eisenberg. 1992. The crystal structure of diphtheria toxin. Nature 357: 216–222.PubMedCrossRefGoogle Scholar
  16. 16.
    Weiss, M.S., S.R. Blanke, R.J. Collier, D. Eisenberg. 1995. Structure of the isolated catalytic domain of diphtheria toxin. Biochem. 34: 773–781.CrossRefGoogle Scholar
  17. 17.
    Stein, P.E., A. Boodhoo, G.D. Armstrong, S.A. Cockle, M.H. Klein, R.J. Read. 1994. The crystal structure of pertussis toxin. Structure 2: 45–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Li, M., F. Dyda, I. Benhar, I. Pastan, D.R. Davies. 1996. The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin. Proc. Natl. Acad. Sci. USA 92: 9308–9312.CrossRefGoogle Scholar
  19. 19.
    Bell, C.E., D. Eisenberg. 1996. Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide. Biochem. 35: 1137–1149.CrossRefGoogle Scholar
  20. 20.
    Ruf, A., J. Mennissier de Murcia, G. de Murcia, G.E. Schulz. 1996. Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken. Proc. Natl. Acad. Sci. USA 93: 7481–7485.PubMedCrossRefGoogle Scholar
  21. 21.
    Takada, T., K. Iida, J. Moss. 1995. Conservation of a common motif in enzymes catalyzing ADP-ribose transfer. Identification of domains in mammalian transferases. J. Biol. Chem. 270: 541–544.PubMedCrossRefGoogle Scholar
  22. 22.
    Koch-Nolte, F., D. Petersen, S. Balasubramanian, F. Haag, D. Kahlke, T. Wilier, R. Kastelein, J.F. Bazan, H.G. Thiele. 1996. Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine/protein mono(ADPribosyl) transferases and share secondary structure motifs with ADP-ribosylating bacterial toxins. J. Biol. Chem. 271: 7686–7693.PubMedCrossRefGoogle Scholar
  23. 23.
    Domenighini, M., R. Rappouli. 1996. Three conserved consensus sequences identify the NAD-binding site of ADP-ribosylating enzymes, expressed by eukaryotes, bacteria and T-even bacteriophages. Molec. Microbiol. 21:661–614.CrossRefGoogle Scholar
  24. 24.
    Murzin, A.G., S.E. Brenner, T. Hubbard, C. Chothia. 1995. SCOP-A Structural Classification Of Proteins database for the investigation of sequences and structures. J. Molec. Biol. 247: 536–540.PubMedGoogle Scholar
  25. 25.
    Holm, L., C. Sander. 1995. Dali-A network tool for protein structure comparison. Trends Biochem. Sci. 20: 478–480.PubMedCrossRefGoogle Scholar
  26. 26.
    Rost, B., C. Sander. 1996. Bridging the protein sequence-structure gap by structure predictions. Ann. Rev. Biophys. Biomolec. Struct. 25: 113–136.CrossRefGoogle Scholar
  27. 27.
    Sayle, R.A., E.J. Milner-White. 1995. Rasmol-Biomolecular graphics for all. Trends Biochem. Sci. 20: 374–376.PubMedCrossRefGoogle Scholar
  28. 28.
    Reich, K.A., G.K. Schoolnik. 1996. Halovibrin, secreted from the light organ symbiont Vibrio fischeri, is a member of a new class of ADP-ribosyltransferases. J. Bacteriol. 178: 209–215.PubMedGoogle Scholar
  29. 29.
    Li, M., F. Dyda, I. Benhar, I. Pastan, D.R. Davies. 1996. Crystal structure of the catalytic domain of Pseudomonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: implications for the activation process and for ADP ribosylation. Proc. Natl. Acad. Sci. USA 93: 6902–6906.PubMedCrossRefGoogle Scholar
  30. 30.
    Sali, A. 1995. Modeling mutations and homologous proteins. Curr. Opin. Biotech. 6: 437–451.PubMedCrossRefGoogle Scholar
  31. 31.
    Levitt, M. 1992. Accurate modeling of protein conformation by automatic segment matching. J. Molec. Biol. 226: 507–533.PubMedCrossRefGoogle Scholar
  32. 32.
    Chung, S.Y., S. Subbiah. 1996. A structural explanation for the twilight zone of protein sequence homology. Structure 4: 1123–1127.PubMedCrossRefGoogle Scholar
  33. 33.
    Domenighini, M., C. Montecucco, W.C. Ripka, R. Rappuoli. 1991. Computer modeling of the NAD binding site of ADP-ribosylating toxins-active site structure and mechanism of NAD binding. Molec. Microbiol. 5: 23.CrossRefGoogle Scholar
  34. 34.
    Marsischky, G.T., B.A. Wilson, R.J. Collier. 1995. Role of glutamic acid 988 of human poly-ADP-ribose polymerase in polymer formation. Evidence for active site similarities to the ADP-ribosylating toxins. J. Biol. Chem. 270: 3247–3254.PubMedCrossRefGoogle Scholar
  35. 35.
    Grimaldi, J.C., S. Balasubramanian, N.H. Kabra, A. Shanafelt, J.F. Bazan, G. Zurawski, M.C. Howard. 1995. CD38-mediated ribosylation of proteins. J. Immunol. 155: 811–817.PubMedGoogle Scholar
  36. 36.
    Prasad, G.S., D.E. McRee, E.A. Stura, D.G. Levitt, H.C. Lee, CD. Stout. 1996. Crystal structure of Aplysia ADP ribosyl cyclase, a homologue of the bifunctional ectoenzyme CD38. Nature Struct. Biol. 3: 957–964.PubMedCrossRefGoogle Scholar
  37. 37.
    Honig, B., A. Nicholls. 1995. Classical electrostatics in biology and chemistry. Science 268: 1144–1149.PubMedCrossRefGoogle Scholar
  38. 38.
    Shao Z., F.H. Arnold. 1996. Engineering new functions and altering existing functions. Curt: Opin. Struct. Biol. 6:513–518.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • J. Fernando Bazan
    • 2
  • Friedrich Koch-Nolte
    • 1
  1. 1.Department of ImmunologyUniversity HospitalHamburgGermany
  2. 2.Department of Molecular BiologyDNAX Research InstitutePalo AltoUSA

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