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.
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References
Bork, P., C. Ouzounis, C. Sander. 1994. From genome sequences to protein function. Cun: Opin. Struct. Biol. 4: 393–403.
Pawson, T. 1995. Protein modules and signalling networks. Nature 373: 573–580.
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.
Holm, L., C. Sander. 1996. Mapping the protein universe. Science 273: 595–603.
Fischer, D., D. Rice, J.U. Bowie, D. Eisenberg. 1996. Assigning amino acid sequences to 3-dimensional protein folds. FASEB J. 10: 126–136.
Rost, B., A. Valencia. 1996. Pitfalls of protein sequence analysis. Cun: Opin. Biotech. 7: 457–461.
Bork, P., T. Gibson. 1996. Applying motif and profile searches. Meth. Enzym. 266: 162–184.
Firestine, S.M., A.E. Nixon, S.J. Benkovic. 1996. Threading your way to protein function. Chem. and Biol. 3: 779–783.
Casari, G., C. Sander, A. Valencia. 1995. A method to predict functional residues in proteins. Nature Struct. Biol. 2: 171–178.
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.
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.
Fauman, E.B., M.A. Saper. 1996. Structure and function of the protein tyrosine phosphatases. Trends Biochem. Sci. 27:413–417.
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.
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.
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.
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.
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.
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.
Bell, C.E., D. Eisenberg. 1996. Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide. Biochem. 35: 1137–1149.
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.
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.
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.
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.
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.
Holm, L., C. Sander. 1995. Dali-A network tool for protein structure comparison. Trends Biochem. Sci. 20: 478–480.
Rost, B., C. Sander. 1996. Bridging the protein sequence-structure gap by structure predictions. Ann. Rev. Biophys. Biomolec. Struct. 25: 113–136.
Sayle, R.A., E.J. Milner-White. 1995. Rasmol-Biomolecular graphics for all. Trends Biochem. Sci. 20: 374–376.
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.
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.
Sali, A. 1995. Modeling mutations and homologous proteins. Curr. Opin. Biotech. 6: 437–451.
Levitt, M. 1992. Accurate modeling of protein conformation by automatic segment matching. J. Molec. Biol. 226: 507–533.
Chung, S.Y., S. Subbiah. 1996. A structural explanation for the twilight zone of protein sequence homology. Structure 4: 1123–1127.
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.
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.
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.
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.
Honig, B., A. Nicholls. 1995. Classical electrostatics in biology and chemistry. Science 268: 1144–1149.
Shao Z., F.H. Arnold. 1996. Engineering new functions and altering existing functions. Curt: Opin. Struct. Biol. 6:513–518.
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Fernando Bazan, J., Koch-Nolte, F. (1997). Sequence and Structural Links between Distant ADP-Ribosyltransferase Families. In: Haag, F., Koch-Nolte, F. (eds) ADP-Ribosylation in Animal Tissues. Advances in Experimental Medicine and Biology, vol 419. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8632-0_12
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DOI: https://doi.org/10.1007/978-1-4419-8632-0_12
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