5dyn | pdb_00005dyn

B. fragilis cysteine protease

spinqualitylabelsall models 5dyn, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dyn is a 2 chain structure with sequence from "bacteroides_inaequalis"_eggerth_and_gagnon_1933 "bacteroides inaequalis" eggerth and gagnon 1933. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, NA Gene: BF9343_2671 ("Bacteroides inaequalis" Eggerth and Gagnon 1933) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Bacteroides fragilis is the leading cause of anaerobic bacteremia and sepsis. Enterotoxigenic strains that produce B. fragilis toxin (BFT, fragilysin) contribute to colitis and intestinal malignancy, yet are also isolated in bloodstream infection. It is not known whether these strains harbor unique genetic determinants that confer virulence in extra-intestinal disease. We demonstrate that BFT contributes to sepsis in mice, and we identify a B. fragilis protease called fragipain (Fpn) that is required for the endogenous activation of BFT through the removal of its auto-inhibitory prodomain. Structural analysis of Fpn reveals a His-Cys catalytic dyad that is characteristic of C11-family cysteine proteases that are conserved in multiple pathogenic Bacteroides spp. and Clostridium spp. Fpn-deficient, enterotoxigenic B. fragilis has an attenuated ability to induce sepsis in mice; however, Fpn is dispensable in B. fragilis colitis, wherein host proteases mediate BFT activation. Our findings define a role for B. fragilis enterotoxin and its activating protease in the pathogenesis of bloodstream infection, which indicates a greater complexity of cellular targeting and activity of BFT than previously recognized. The expression of fpn by both toxigenic and nontoxigenic strains suggests that this protease may contribute to anaerobic sepsis in ways that extend beyond its role in toxin activation. It could thus potentially serve as a target for disease modification. Activation of Bacteroides fragilis toxin by a novel bacterial protease contributes to anaerobic sepsis in mice.,Choi VM, Herrou J, Hecht AL, Teoh WP, Turner JR, Crosson S, Bubeck Wardenburg J Nat Med. 2016 May;22(5):563-7. doi: 10.1038/nm.4077. Epub 2016 Apr 18. PMID:27089515 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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