title: Structure of the ecto-ADP-ribosyl transferase ART2.2 from rat.
abstract: The mammalian extracellular ADP-ribosyl transferases ART1 through ART5 are sequence-related to each other. Among them ART2 is involved in immuno regulation. The variant ART2.2 was expressed in the periplasm of Escherichia coli and crystallized. Its structure was determined by X-ray diffraction at 1.7A resolution in one crystal form and at slightly lower resolutions in two others. The active center was indicated by a ligated nicotinamide analogue, which also revealed a small induced-fit. The centerpiece of the chainfold of ART2.2 agrees with those of all bacterial ADP-ribosyl transferases. This correspondence and the nicotinamide position were used to model the binding structure of the whole substrate NAD(+) at ART2.2. Two of the bacterial enzymes are structurally more closely related to ART2.2 while the others are more closely related to the eukaryotic poly(ADP-ribosyl)polymerase. This splits the ADP-ribosyl transferases into two distinct subfamilies. A special feature of ART2.2 is its long N-terminal extension and two disulfide bridges that are far away from the active center. They stabilize the protein against denaturation and presumably also against shearing forces parallel with the membrane where ART2.2 is anchored.
authors.affiliation: Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Freiburg 79104, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller-Dieckmann
authors.forename: Holger
authors.initials: H
authors.lastname: Ritter
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
authors.forename: Georg E
authors.initials: GE
authors.lastname: Schulz
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat