The art of blocking ADP-ribosyltransferases (ARTs): nanobodies as experimental and therapeutic tools to block mammalian and toxin ARTs

FEBS J. 2013 Aug;280(15):3543-50. doi: 10.1111/febs.12313. Epub 2013 Jun 14.


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.

Keywords: ADP-ribosyltransferase; enzyme inhibitor; nanobody; recombinant antibody; single-domain antibody; toxin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP Ribose Transferases / antagonists & inhibitors*
  • ADP Ribose Transferases / metabolism
  • Amino Acid Sequence
  • Animals
  • Bacterial Infections / drug therapy
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / metabolism
  • Camelids, New World
  • Drug Delivery Systems
  • Humans
  • Molecular Sequence Data
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / pharmacology*
  • Virulence Factors / antagonists & inhibitors
  • Virulence Factors / metabolism


  • Bacterial Toxins
  • Single-Domain Antibodies
  • Virulence Factors
  • ADP Ribose Transferases
  • spvB protein, Salmonella enterica virulence plasmid