Larvin: The characterization of a novel mono-ADP-ribosyltransferase toxin

Abstract

Mono-ADP-ribosyltransferase (mART) toxins are a class of bacterial proteins which function by cleaving the nicotinamide moiety from NAD+ and attaching the ADP-ribose to a host protein, to alter its function. These are important virulence factors for many diseases. Larvin is a novel mART toxin from Paenibacillus larvae, the causative agent of American Foulbrood in honey bees. Larvin targets RhoA as a substrate for its transferase reaction, and kinetics for the RhoA substrate were characterized for the first time for the mART C3 subgroup. A small molecule inhibitor of Larvin enzymatic activity was discovered, the first known inhibitor for C3 toxins. Larvin was crystallized, and its crystal structure was solved to 2.3 Å resolution. Larvin was also shown to have a different mechanism of cell entry from other C3 toxins. Characterization of Larvin allows for a fuller understanding of the mART family, and for development of better inhibitors as potential therapeutics.