4fml | pdb_00004fml

Catalytic domain of VahC from Aeromonas hydrophila

spinqualitylabelsall models 4fml, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fml is a 3 chain structure with sequence from "aeromonas_liquefaciens"_kluyver_and_van_niel_1936 "aeromonas liquefaciens" kluyver and van niel 1936. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3nts Gene: VahC, vsdC ("Aeromonas liquefaciens" Kluyver and van Niel 1936) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The mono-ADP-ribosyltransferase (mART) toxins are contributing factors to a number of human diseases, including cholera, diphtheria, traveler's diarrhea, and whooping cough. VahC is a cytotoxic, actin-targeting mART from Aeromonas hydrophila PPD134/91. This bacterium is implicated primarily in diseases among freshwater fish species but also contributes to gastrointestinal and extraintestinal infections in humans. VahC was shown to ADP-ribosylate Arg-177 of actin, and the kinetic parameters were K(m)(NAD(+)) = 6 muM, K(m)(actin) = 24 muM, and k(cat) = 22 s(-1). VahC activity caused depolymerization of actin filaments, which induced caspase-mediated apoptosis in HeLa Tet-Off cells. Alanine-scanning mutagenesis of predicted catalytic residues showed the predicted loss of in vitro mART activity and cytotoxicity. Bioinformatic and kinetic analysis also identified three residues in the active site loop that were critical for the catalytic mechanism. A 1.9 A crystal structure supported the proposed roles of these residues and their conserved nature among toxin homologues. Several small molecules were characterized as inhibitors of in vitro VahC mART activity and suramin was the best inhibitor (IC(50) = 20 muM). Inhibitor activity was also characterized against two other actin-targeting mART toxins. Notably, these inhibitors represent the first report of broad spectrum inhibition of actin-targeting mART toxins. Characterization of an actin-targeting ADP-ribosyltransferase from Aeromonas hydrophila.,Shniffer A, Visschedyk DD, Ravulapalli R, Suarez G, Turgeon ZJ, Petrie AA, Chopra AK, Merrill AR J Biol Chem. 2012 Oct 26;287(44):37030-41. doi: 10.1074/jbc.M112.397612. Epub, 2012 Sep 11. PMID:22969084 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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