title: Crystal structure of the Clostridium limosum C3 exoenzyme.
abstract: C3-like toxins ADP-ribosylate and inactivate Rho GTPases. Seven C3-like ADP-ribosyltransferases produced by Clostridium botulinum, Clostridium limosum, Bacillus cereus and Staphylococcus aureus were identified and two representatives--C3bot from C. botulinum and C3stau2 from S. aureus--were crystallized. Here we present the 1.8A structure of C. limosum C3 transferase C3lim and compare it to the structures of other family members. In contrast to the structure of apo-C3bot, the canonical ADP-ribosylating turn turn motif is observed in a primed conformation, ready for NAD binding. This suggests an impact on the binding mode of NAD and on the transferase reaction. The crystal structure explains why auto-ADP-ribosylation of C3lim at Arg41 interferes with the ADP-ribosyltransferase activity of the toxin.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Vogelsgesang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stieglitz
authors.forename: Christian
authors.initials: C
authors.lastname: Herrmann
authors.forename: Alex
authors.initials: A
authors.lastname: Pautsch
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins