title: Photox, a novel actin-targeting mono-ADP-ribosyltransferase from Photorhabdus luminescens.
abstract: Photorhabdus luminescens is a pathogenic bacterium that produces many toxic proteins. The mono-ADP-ribosyltransferases (mARTs) are an enzyme class produced by numerous pathogenic bacteria and participate in disease in plants and animals, including humans. Herein we report a novel mART from P. luminescens called Photox. This 46-kDa toxin shows high homology to other actin-targeting mARTs in hallmark catalytic regions and a similar core catalytic fold. Furthermore, Photox shows in vivo cytotoxic activity against yeast, with protection occurring when catalytic residues are substituted with alanine. In vitro, enzymatic activity (k(cat), 1680 +/- 75 min(-1)) is higher than that of the related iota toxin, and diminishes by nearly 14,000-fold following substitution of the catalytic Glu (E355A). This toxin specifically ADP-ribosylates monomeric alpha-skeletal actin and nonmuscle beta- and gamma-actin at Arg(177), inhibiting regular polymerization of actin filaments. These results indicate that Photox is indeed an ADP-ribosyltransferase, making it the newest member of the actin-targeting mART family.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Visschedyk
authors.forename: Alexandru A
authors.initials: AA
authors.lastname: Perieteanu
authors.forename: Zachari J
authors.initials: ZJ
authors.lastname: Turgeon
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fieldhouse
authors.forename: John F
authors.initials: JF
authors.lastname: Dawson
authors.forename: A Rod
authors.initials: AR
authors.lastname: Merrill
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D020637:Photorhabdus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D010935:Plant Diseases / Q000382:microbiology
chemical_list: D000199:Actins; D001427:Bacterial Toxins; D036002:ADP Ribose Transferases