title: The art of blocking ADP-ribosyltransferases (ARTs): nanobodies as experimental and therapeutic tools to block mammalian and toxin ARTs.
abstract: In 1901, the first Nobel Prize in Physiology or Medicine was awarded to Emil von Behring for his ground-breaking discovery of serum therapy: serum from horses vaccinated with toxin-containing culture medium of Corynebacterium diphtheriae contained life-saving 'antitoxins'. The molecular nature of the ADP-ribosylating toxin and the neutralizing antibodies were unraveled only 50 years later. Today, von Behring's antibody therapy is being refined with a new generation of recombinant antibodies and antibody fragments. Nanobodies, which are single-domain antibodies derived from the peculiar heavy-chain antibodies of llamas and other camelids, are emerging as a promising new class of highly specific enzyme inhibitors. In this review, we illustrate the potential of nanobodies as tools to block extracellular and intracellular ADP-ribosyltransferases (ARTs), using the toxin-related membrane-bound mammalian ecto-enzyme ARTC2 and the actin-ADP-ribosylating Salmonella virulence plasmid factor B toxin of Salmonella enterica as examples.
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.forename: Björn
authors.initials: B
authors.lastname: Rissiek
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Goldbaum
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
mesh_terms: D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002161:Camelids, New World; D016503:Drug Delivery Systems; D006801:Humans; D008969:Molecular Sequence Data; D061905:Single-Domain Antibodies / Q000737:chemistry / Q000494:pharmacology*; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D061905:Single-Domain Antibodies; D037521:Virulence Factors; D036002:ADP Ribose Transferases; C415223:spvB protein, Salmonella enterica virulence plasmid
keywords: ADP-ribosyltransferase; enzyme inhibitor; nanobody; recombinant antibody; single-domain antibody; toxin