Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase from Bacillus cereus

Abstract

Background: Cethrax toxin from B. cereus inactivates mammalian cells through cytoplasmic ADP-ribosyltransferase activity. Results: The crystal structure of Certhrax reveals that it has two domains, one that binds protective antigen and another that has ADP-ribosyltransferase activity. Conclusion: Good inhibitors against the ADP-ribosyltransferase activity have been developed. Significance: Certhrax may be an important virulence factor in B. cereus pathogenesis.

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

“…2D). This is consistent with other mART toxins, such as Certhrax toxin, which has a K m of 42 Ϯ 11 M and a k cat of 8.7 Ϯ 1.0 min Ϫ1 (23). Although some mART toxins do not possess GH activity, most have GH activity that is typically lower than their transferase activity (1).…”

“…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).…”

“…These compounds, PJ34, P6-C, P6-D, P6-E, and P6-F (Fig. 4), are known inhibitors of other mART toxins (23,25). Lineweaver-Burk analysis was performed for kinetic inhibition data of Scabin with PJ34 inhibitor to validate the mechanism of inhibition for the P-series inhibitors.…”

Assembly and Function of the Bacillus anthracis S-Layer

“…pBC210 carries an atxA -like gene ( atxA2 ) that contributes to the pathogenesis of anthrax-like disease in B. cereus G9241 (125). pBC210 also carries pag2 (60% identity with pag ) and lef 2 (36% identity with lef ) (Figure 1); the lef 2 product shows the presence of a putative PA binding domain; however, the metalloprotease domain of LF is replaced with an ADP-ribosyltransferase domain (41, 143). The lef 2 product, which has been designated Certhrax, is translocated by PA2 into host cells, modifies the host factor vinculin, and disrupts focal adhesion complexes (131, 143).…”

“…pBC210 also carries pag2 (60% identity with pag ) and lef 2 (36% identity with lef ) (Figure 1); the lef 2 product shows the presence of a putative PA binding domain; however, the metalloprotease domain of LF is replaced with an ADP-ribosyltransferase domain (41, 143). The lef 2 product, which has been designated Certhrax, is translocated by PA2 into host cells, modifies the host factor vinculin, and disrupts focal adhesion complexes (131, 143). These features of B. anthracis and B. cereus may account for the observed variation in disease severity and geographic spread associated with spores causing anthrax or anthrax-like disease.…”