title: 1H, 13C, and 15N resonance assignments of an enzymatically active domain from the catalytic component (CDTa, residues 216-420) of a binary toxin from Clostridium difficile.
abstract: Clostridium difficile is a bacterial pathogen and is the most commonly reported source of nosocomial infection in industrialized nations. Symptoms of C. difficile infection (CDI) include antibiotic-associated diarrhea, pseudomembranous colitis, sepsis and death. Over the last decade, rates and severity of hospital infections in North America and Europe have increased dramatically and correlate with the emergence of a hypervirulent strain of C. difficile characterized by the presence of a binary toxin, CDT (C. difficile toxin). The binary toxin consists of an enzymatic component (CDTa) and a cellular binding component (CDTb) that together form the active binary toxin complex. CDTa harbors a pair of structurally similar but functionally distinct domains, an N-terminal domain (residues 1-215; (1-215)CDTa) that interacts with CDTb and a C-terminal domain (residues 216-420; (216-420)CDTa) that harbors the intact ADP-ribosyltransferase (ART) active site. Reported here are the (1)H, (13)C, and (15)N backbone resonance assignments of the 23 kDa, 205 amino acid C-terminal enzymatic domain of CDTa, termed (216-420)CDTa. These NMR resonance assignments for (216-420)CDTa represent the first for a family of ART binary toxins and provide the framework for detailed characterization of the solution-state protein structure determination, dynamic studies of this domain, as well as NMR-based drug discovery efforts.
authors.affiliation: Center for Biomolecular Therapeutics (CBT), Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD, 21201, USA.
authors.forename: Braden M
authors.initials: BM
authors.lastname: Roth
authors.affiliation: Center for Biomolecular Therapeutics (CBT), Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD, 21201, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Godoy-Ruiz
authors.affiliation: Center for Biomolecular Therapeutics (CBT), Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD, 21201, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Varney
authors.affiliation: Department of Vaccine Analytical Development, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA, 19486, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Rustandi
authors.affiliation: Center for Biomolecular Therapeutics (CBT), Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD, 21201, USA. dweber@som.umaryland.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry*; D020134:Catalytic Domain; D016360:Clostridioides difficile / Q000201:enzymology*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D001427:Bacterial Toxins
keywords: ADP-ribosyltransferase; Binary toxin; CDI; CDTa; Clostridium difficile