title: Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases.
abstract: Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences--including a primary sequence pattern--to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data--and we need high-throughput validation--our approach provides insight into the newest toxin ADP-ribosyltransferases.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fieldhouse
authors.forename: Zachari
authors.initials: Z
authors.lastname: Turgeon
authors.forename: Dawn
authors.initials: D
authors.lastname: White
authors.forename: A Rod
authors.initials: AR
authors.lastname: Merrill
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001409:Bacillus cereus / Q000737:chemistry / Q000201:enzymology* / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology; D057225:Data Mining; D013293:Enterococcus faecalis / Q000737:chemistry / Q000201:enzymology / Q000472:pathogenicity; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009162:Mycobacterium avium / Q000737:chemistry / Q000201:enzymology / Q000472:pathogenicity; D020637:Photorhabdus / Q000737:chemistry / Q000201:enzymology / Q000472:pathogenicity; D010802:Phylogeny; D011487:Protein Conformation; D015203:Reproducibility of Results; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D014733:Vibrio / Q000737:chemistry / Q000201:enzymology / Q000472:pathogenicity; D014734:Vibrio cholerae / Q000737:chemistry / Q000201:enzymology* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D036002:ADP Ribose Transferases; C578090:certhrax toxin, Bacillus cereus