C3larvin Toxin, an ADP-ribosyltransferase from Paenibacillus larvae

Abstract

Background: C3larvin toxin from P. larvae modifies RhoA protein through its ADP-ribosyltransferase activity. Results: The crystal structure of C3larvin reveals that it is a single domain toxin/enzyme in the C3 subclass. Conclusion: A lead inhibitor of the ADP-ribosyltransferase activity has been developed. Significance: C3larvin may be an important virulence factor in P. larvae pathogenesis.

Molecular pathogenesis of American Foulbrood: how Paenibacillus larvae kills honey bee larvae

“…The third toxin of P. larvae, C3larvin, has been identified via a bioinformatic strategy in the draft genome sequence of BRL230010 [42 ]. C3larvin was shown to be a mART toxin with glycohydrolase and transferase activities targeting RhoA.…”

ADP-ribosylating toxins modifying the actin cytoskeleton

“…The recently described C3larvin is derived from P. larvae, the etiological agent of American foulbrood in honeybees [23]. It is still too early to know if C3larvin is a virulence factor employed by this bacterium during disease, which includes spore ingestion and germination in the larval gut that leads to subsequent consumption of the larvae by the metabolically active, vegetative P. larvae.…”

“…Two isoforms, C3bot1 and C3bot2, have subsequently been characterized and share 60% sequence identity. C3 and related C3-like molecules are approximately 25 kDa, basic (pI > 9) proteins also produced by other Gram-positive bacteria, such as Clostridium limosum (C3lim), Bacillus cereus (C3cer), Paenibacillus larvae (C3larvin), and Staphylococcus aureus (Cstau) [23,24]. The C3-related enzyme produced by S. aureus is also called epithelial differentiation inhibitor (EDIN), or C3stau, and consists of three isoforms (A, B, C) sharing about 35% sequence identity with C. botulinum C3.…”

Scabin, a Novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies

“…Although some mART toxins do not possess GH activity, most have GH activity that is typically lower than their transferase activity (1). An active site variant of Scabin was prepared that involved replacing the QXE catalytic signature with AXA, which has been shown previously to render mART toxins catalytically impotent (5,23). The catalytic Q158A/E160A variant was significantly less active, as anticipated for replacement of this key catalytic signature in mART toxins, and gave a k cat of 0.31 Ϯ 0.02 min Ϫ1 ( Table 2).…”

“…Examples of mART toxins include ExoA from Pseudomonas aeruginosa, pertussis toxin from Bordetella pertussis, C3larvin from Paenibacillus larvae, and Pierisin-1 from Pieris rapae (3)(4)(5). Quite often, mART toxins target protein residues, such as Arg, Asn, and Cys (6).…”