title: Sequence and structural links between distant ADP-ribosyltransferase families.
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-ribosyl-transferase (ADPRT) catalytic domain. The major features of this protein fold have recurred in the more recently solved crystal structures of the cholera toxin-related heat-labile enterotoxin (LT), diphtheria toxin (DT) and pertussis toxin (PT). A core set of alpha + beta 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.
authors.affiliation: Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304-1104, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Bazan
authors.forename: F
authors.initials: F
authors.lastname: Koch-Nolte
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D043525:Cytosine Deaminase; D008969:Molecular Sequence Data; D009700:Nucleoside Deaminases / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000145:classification; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D011065:Poly(ADP-ribose) Polymerases; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase