Structural highlights
Function[CRAX_BACCE] A probable mono(ADP-ribosyl)transferase; it is not known which residue is targeted for ADP-ribosylation. Upon expression in yeast cells causes cell death.[1] Publication Abstract from PubMedWe identified Certhrax, the first anthrax-like mART toxin from the pathogenic G9241 strain of Bacillus cereus. Certhrax shares 31% sequence identity with anthrax lethal factor from Bacillus anthracis, however, we have shown that the toxicity of Certhrax resides in the mART domain, while anthrax uses a metalloprotease mechanism. Like anthrax lethal factor, Certhrax was found to require protective antigen for host cell entry. This two-domain enzyme was shown to be 60-fold more toxic to mammalian cells than anthrax lethal factor. Certhrax localizes to distinct regions within mouse RAW264.7 cells by 10 min post-infection and is extranuclear in its cellular location. Substitution of catalytic residues shows that the mART function is responsible for the toxicity, and it binds NAD+ with high affinity (KD = 52.3 +/- 12.2 muM). We report the 2.2 A Certhrax structure, highlighting its structural similarities and differences with anthrax lethal factor. We also determined the crystal structures of two good inhibitors (P6, KD = 1.7 +/- 0.2 muM, Ki = 1.8 +/- 0.4 muM; and PJ34, KD = 5.8 +/- 2.6 muM, Ki = 9.6 +/- 0.3 muM) in complex with Certhrax. As with other toxins in this family, the phosphate-nicotinamide loop moves toward the NAD+ binding site with bound inhibitor. These results indicate that Certhrax may be important in the pathogenesis of B. cereus. Certhrax toxin, an Anthrax-related ADP-ribosyltransferase from Bacillus cereus.,Visschedyk D, Rochon A, Tempel W, Dimov S, Park HW, Merrill AR J Biol Chem. 2012 Sep 19. PMID:22992735[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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