Genomes and Genes
adp ribose transferases
Summary: Enzymes that transfer the ADP-RIBOSE group of NAD or NADP to proteins or other small molecules. Transfer of ADP-ribose to water (i.e., hydrolysis) is catalyzed by the NADASES. The mono(ADP-ribose)transferases transfer a single ADP-ribose. POLY(ADP-RIBOSE) POLYMERASES transfer multiple units of ADP-ribose to protein targets, building POLY ADENOSINE DIPHOSPHATE RIBOSE in linear or branched chains.
- Fieldhouse R, Merrill A. Needle in the haystack: structure-based toxin discovery. Trends Biochem Sci. 2008;33:546-56 pubmed publisher..However, a newly developed tactic, in which fold recognition dominates, reduces reliance on sequence similarity and advances scientists toward a true structure-based protein-family expansion methodology. ..
- Cisz M, Lee P, Rietsch A. ExoS controls the cell contact-mediated switch to effector secretion in Pseudomonas aeruginosa. J Bacteriol. 2008;190:2726-38 pubmed..The requirement for a host cell cofactor to control effector secretion may help explain the recently observed phenomenon of target cell specificity in both the Yersinia and P. aeruginosa type III secretion systems. ..
- Barth H, Stiles B. Binary actin-ADP-ribosylating toxins and their use as molecular Trojan horses for drug delivery into eukaryotic cells. Curr Med Chem. 2008;15:459-69 pubmed..This review will focus on the recent progress in studying binary actin ADP-ribosylating toxins as highly effective virulence factors and innovative tools for cell physiology as well as pharmacology. ..
- Aktories K, Schwan C, Papatheodorou P, Lang A. Bidirectional attack on the actin cytoskeleton. Bacterial protein toxins causing polymerization or depolymerization of actin. Toxicon. 2012;60:572-81 pubmed publisher..By contrast, actin polymerization is facilitated by the tripartite Photorhabdus luminescens toxin complex including TccC3, which modifies actin at threonine-148. The review discusses both toxin families in respect to recent findings. ..
- Baysarowich J, Koteva K, Hughes D, Ejim L, Griffiths E, Zhang K, et al. Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr. Proc Natl Acad Sci U S A. 2008;105:4886-91 pubmed publisher..This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic. ..
- Weldon J, Xiang L, Chertov O, Margulies I, Kreitman R, FitzGerald D, et al. A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood. 2009;113:3792-800 pubmed publisher..We conclude that HA22-LR advances the therapeutic efficacy of HA22 by using an approach that may be applicable to other PE-based immunotoxins. ..
- Garey K, Vo Q, LaRocco M, Gentry L, Tam V. Prevalence of type III secretion protein exoenzymes and antimicrobial susceptibility patterns from bloodstream isolates of patients with Pseudomonas aeruginosa bacteremia. J Chemother. 2008;20:714-20 pubmed..One of two type III secretion effector proteins were almost universally present in PSA bloodstream isolates. Isolates containing the exoU gene were more likely to be resistant to multiple antibiotics. ..
- Kaiser E, Pust S, Kroll C, Barth H. Cyclophilin A facilitates translocation of the Clostridium botulinum C2 toxin across membranes of acidified endosomes into the cytosol of mammalian cells. Cell Microbiol. 2009;11:780-95 pubmed publisher..In conclusion, our results suggest an essential role of cyclophilin A for translocation of C2I across endosomal membranes during the uptake of C2 toxin into mammalian cells. ..
- Turgeon Z, White D, Jørgensen R, Visschedyk D, Fieldhouse R, Mangroo D, et al. Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett. 2009;300:97-106 pubmed publisher..Finally, the NAP inhibitor shows therapeutic protective effects against toxin invasion of mammalian cells, including human lung cells. ..
- Deng Q, Barbieri J. Modulation of host cell endocytosis by the type III cytotoxin, Pseudomonas ExoS. Traffic. 2008;9:1948-57 pubmed publisher..The ability ADPr to inhibit mammalian vesicle trafficking provides a new mechanism for bacterial toxin-mediated virulence. ..
- Kleine H, Poreba E, Lesniewicz K, Hassa P, Hottiger M, Litchfield D, et al. Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation. Mol Cell. 2008;32:57-69 pubmed publisher..This mechanism explains why the novel PARPs are unable to function as polymerases. This discovery will help to illuminate the different biological functions of mono- versus poly-ADP-ribosylation in cells. ..
- Del Vecchio M, Pogni R, Baratto M, Nobbs A, Rappuoli R, Pizza M, et al. Identification of an iron-sulfur cluster that modulates the enzymatic activity in NarE, a Neisseria meningitidis ADP-ribosyltransferase. J Biol Chem. 2009;284:33040-7 pubmed publisher..This is the first observation suggesting that a member of the ADP-ribosyltransferase family contains an Fe-S cluster implicated in catalysis. This observation may unravel novel functions exerted by this class of enzymes. ..
- Suarez G, Sierra J, Erova T, Sha J, Horneman A, Chopra A. A type VI secretion system effector protein, VgrG1, from Aeromonas hydrophila that induces host cell toxicity by ADP ribosylation of actin. J Bacteriol. 2010;192:155-68 pubmed publisher..hydrophila possessed actin ADPRT activity associated with its VIP-2 domain and that this domain alone was able to induce a rounded phenotype in HeLa Tet-Off cells, followed by apoptosis mediated by caspase 9 activation...
- Jørgensen R, Purdy A, Fieldhouse R, Kimber M, Bartlett D, Merrill A. Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae. J Biol Chem. 2008;283:10671-8 pubmed publisher..These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment. ..
- Hottiger M, Hassa P, Luscher B, Schüler H, Koch Nolte F. Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem Sci. 2010;35:208-19 pubmed publisher..A unified nomenclature would facilitate communication between researchers both inside and outside the ADP-ribosylation field. ..
- Sha J, Wang S, Suarez G, Sierra J, Fadl A, Erova T, et al. Further characterization of a type III secretion system (T3SS) and of a new effector protein from a clinical isolate of Aeromonas hydrophila--part I. Microb Pathog. 2007;43:127-46 pubmed..Finally, we detected specific anti-AexU antibodies in the sera of mice that survived challenge by the WT bacterium, which may indicate that AexU plays an important role in the pathogenesis of Aeromonas infections. ..
- Carette J, Guimaraes C, Varadarajan M, Park A, Wuethrich I, Godarova A, et al. Haploid genetic screens in human cells identify host factors used by pathogens. Science. 2009;326:1231-5 pubmed publisher..This approach has both conceptual and practical parallels with genetic approaches in haploid yeast. ..
- Dani N, Mayo E, Stilla A, Marchegiani A, Di Paola S, Corda D, et al. Mono-ADP-ribosylation of the G protein betagamma dimer is modulated by hormones and inhibited by Arf6. J Biol Chem. 2011;286:5995-6005 pubmed publisher..These data provide further understanding of the mechanisms that regulate endogenous ADP-ribosylation of the G? subunit, and they demonstrate a novel role for Arf6 in hormone regulation of G? subunit mono-ADP-ribosylation. ..
- Uchida I, Ishihara R, Tanaka K, Hata E, Makino S, Kanno T, et al. Salmonella enterica serotype Typhimurium DT104 ArtA-dependent modification of pertussis toxin-sensitive G proteins in the presence of [32P]NAD. Microbiology. 2009;155:3710-8 pubmed publisher..Hydrogen peroxide, an oxidative stressor, also induced ArtA/ArtB production, suggesting that these agents induce in vivo synthesis of ArtA/ArtB. These results, taken together, suggest that ArtA/ArtB is an active toxin similar to PTX. ..
- Alderson R, Kreitman R, Chen T, Yeung P, Herbst R, Fox J, et al. CAT-8015: a second-generation pseudomonas exotoxin A-based immunotherapy targeting CD22-expressing hematologic malignancies. Clin Cancer Res. 2009;15:832-9 pubmed publisher..CAT-8015 is a CD22-targeting immunotoxin that, in preclinical studies, has greatly improved efficacy compared with CAT-3888. ..
- Koch Nolte F, Kernstock S, Mueller Dieckmann C, Weiss M, Haag F. Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases. Front Biosci. 2008;13:6716-29 pubmed..Recently, molecular cloning, site directed mutagenesis and three-dimensional structural analyses of prototype mammalian ARTs and ARHs have shed fresh insight into the structure and function of these intriguing enzymes. ..
- Papatheodorou P, Wilczek C, Nölke T, Guttenberg G, Hornuss D, Schwan C, et al. Identification of the cellular receptor of Clostridium spiroforme toxin. Infect Immun. 2012;80:1418-23 pubmed publisher..Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor...
- Lang A, Schmidt G, Schlosser A, Hey T, Larrinua I, Sheets J, et al. Photorhabdus luminescens toxins ADP-ribosylate actin and RhoA to force actin clustering. Science. 2010;327:1139-42 pubmed publisher..The concerted action of both toxins inhibited phagocytosis of target insect cells and induced extensive intracellular polymerization and clustering of actin. Several human pathogenic bacteria produce related toxins. ..
- Visschedyk D, Perieteanu A, Turgeon Z, Fieldhouse R, Dawson J, Merrill A. Photox, a novel actin-targeting mono-ADP-ribosyltransferase from Photorhabdus luminescens. J Biol Chem. 2010;285:13525-34 pubmed publisher..These results indicate that Photox is indeed an ADP-ribosyltransferase, making it the newest member of the actin-targeting mART family...
- ..Recent findings by three groups (Ahel et al., 2009; Gottschalk et al., 2009; Timinszky et al., 2009) establish that proteins with macrodomains bind poly-ADP-ribose to mediate the cellular response to DNA damage. ..
- Fahrer J, Kuban J, Heine K, Rupps G, Kaiser E, Felder E, et al. Selective and specific internalization of clostridial C3 ADP-ribosyltransferases into macrophages and monocytes. Cell Microbiol. 2010;12:233-47 pubmed publisher..5). In conclusion, we identified macrophages/monocytes as target cells for clostridial C3 transferases and shed light on their selective uptake mechanism, which might contribute to understand the role of C3 transferases in pathogenesis. ..
- Rohrbeck A, Kolbe T, Hagemann S, Genth H, Just I. Distinct biological activities of C3 and ADP-ribosyltransferase-deficient C3-E174Q. FEBS J. 2012;279:2657-71 pubmed publisher..While morphological changes and anti-apoptotic activity strictly depend on ADP-ribosyltransferase activity, the anti-proliferative effects are independent of ADP-ribosyltransferase activity. ..
- Carter G, Lyras D, Allen D, Mackin K, Howarth P, O Connor J, et al. Binary toxin production in Clostridium difficile is regulated by CdtR, a LytTR family response regulator. J Bacteriol. 2007;189:7290-301 pubmed
- Tsuge H, Nagahama M, Oda M, Iwamoto S, Utsunomiya H, Marquez V, et al. Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens iota-toxin. Proc Natl Acad Sci U S A. 2008;105:7399-404 pubmed publisher..Our results suggest a common reaction mechanism for ADPRTs. Moreover, the structure might be of use in rational drug design to block toxin-substrate recognition. ..
- Hritonenko V, Evans D, Fleiszig S. Translocon-independent intracellular replication by Pseudomonas aeruginosa requires the ADP-ribosylation domain of ExoS. Microbes Infect. 2012;14:1366-73 pubmed publisher..These data suggest that T3SS effectors can participate in pathogenesis without translocon-mediated translocation across host membranes, and that intracellular bacteria can contribute to P. aeruginosa pathogenesis within epithelial cells...
- Sundriyal A, Roberts A, Shone C, Acharya K. Structural basis for substrate recognition in the enzymatic component of ADP-ribosyltransferase toxin CDTa from Clostridium difficile. J Biol Chem. 2009;284:28713-9 pubmed publisher..These structural data provide the first detailed information on protein-donor substrate complex stabilization in CDTa, which may have implications in understanding CDT recognition. ..
- Okuda J, Okamoto M, Hayashi N, Sawada S, Minagawa S, Gotoh N. Complementation of the exoS gene in the pvdE pyoverdine synthesis gene-deficient mutant of Pseudomonas aeruginosa results in recovery of the pvdE gene-mediated penetration through the intestinal epithelial cell barrier but not the pvdE-mediated virul. J Infect Chemother. 2012;18:332-40 pubmed publisher
- Balducci E, Micossi L, Soldaini E, Rappuoli R. Expression and selective up-regulation of toxin-related mono ADP-ribosyltransferases by pathogen-associated molecular patterns in alveolar epithelial cells. FEBS Lett. 2007;581:4199-204 pubmed..These results show that human ARTs possess a differential capacity to respond to bacteria cell wall components and might play a crucial role in innate immune response in airways. ..
- Barth H, Aktories K. New insights into the mode of action of the actin ADP-ribosylating virulence factors Salmonella enterica SpvB and Clostridium botulinum C2 toxin. Eur J Cell Biol. 2011;90:944-50 pubmed publisher..This review summarizes recent findings of research on the actin ADP-ribosylating toxins regarding their cellular uptake, molecular mode of action and the cellular consequences following ADP-ribosylation of actin. ..
- Ménétrey J, Flatau G, Boquet P, Ménez A, Stura E. Structural basis for the NAD-hydrolysis mechanism and the ARTT-loop plasticity of C3 exoenzymes. Protein Sci. 2008;17:878-86 pubmed publisher..Altogether, these structures expand our understanding of the conformational diversity of the C3 exoenzyme, mainly within the ARTT loop. ..
- Gibert M, Monier M, Ruez R, Hale M, Stiles B, Benmerah A, et al. Endocytosis and toxicity of clostridial binary toxins depend on a clathrin-independent pathway regulated by Rho-GDI. Cell Microbiol. 2011;13:154-70 pubmed publisher..Accordingly, the intracellular effects of Iota and C2 on the cytoskeleton were inhibited by inactivation of dynamin or by Rho-GDI whereas inhibitors of clathrin-dependent endocytosis had no protective effect. ..
- Wang Y, Li J, Hou S, Wang X, Li Y, Ren D, et al. A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabidopsis mitogen-activated protein kinase kinases. Plant Cell. 2010;22:2033-44 pubmed publisher..Arg-313 of MKK5 is required for ADP-ribosylation by HopF2 and MKK5 function in the plant cell. Together, these results indicate that MKKs are important targets of HopF2. ..
- Hansen J, Weldon J, Xiang L, Beers R, Onda M, Pastan I. A recombinant immunotoxin targeting CD22 with low immunogenicity, low nonspecific toxicity, and high antitumor activity in mice. J Immunother. 2010;33:297-304 pubmed publisher..Future studies will determine if these properties carry over to humans with cancer. ..
- Ferrell E, Carty N, Colmer Hamood J, Hamood A, West S. Regulation of Pseudomonas aeruginosa ptxR by Vfr. Microbiology. 2008;154:431-9 pubmed publisher..Our results suggest that Vfr modulates toxA and lasB expression in PAO1 through PtxR. A model defining the relationships between these different genes is presented. ..
- Adriouch S, Bannas P, Schwarz N, Fliegert R, Guse A, Seman M, et al. ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. FASEB J. 2008;22:861-9 pubmed..ADP-ribose shares an adenine-ribonucleotide moiety with ATP. Our results indicate that ADP-ribosylation of R125 positions this common chemical framework to fit into the nucleotide-binding site of P2X7 and thereby gates the channel. ..
- Li W, Lyte M, Freestone P, Ajmal A, Colmer Hamood J, Hamood A. Norepinephrine represses the expression of toxA and the siderophore genes in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2009;299:100-9 pubmed publisher..aeruginosa independent of pyoverdine. Thus, norepinephrine apparently influences the pathogenesis of P. aeruginosa by affecting its pattern of growth and the production of virulence factors...
- Bachran C, Sutherland M, Bachran D, Fuchs H. Quantification of diphtheria toxin mediated ADP-ribosylation in a solid-phase assay. Clin Chem. 2007;53:1676-83 pubmed..The assay may be the basis for the development of a routine diagnostic assay for the detection of DT activity and highly specific inhibitors of DT. ..
- Wang H, Liang Q, Cao K, Ge X. Endogenous protein mono-ADP-ribosylation in Arabidopsis thaliana. Planta. 2011;233:1287-92 pubmed publisher..Although the substrate proteins remain to be identified, this is the first report on the characterization of endogenously mono-ADP-ribosylated proteins in plants. ..
- Weldon J, Pastan I. A guide to taming a toxin--recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancer. FEBS J. 2011;278:4683-700 pubmed publisher..This review summarizes our current understanding of PE, its intoxication pathway, and the ongoing efforts to convert this toxin into a treatment for cancer. ..
- Angus A, Evans D, Barbieri J, Fleiszig S. The ADP-ribosylation domain of Pseudomonas aeruginosa ExoS is required for membrane bleb niche formation and bacterial survival within epithelial cells. Infect Immun. 2010;78:4500-10 pubmed publisher..aeruginosa bleb niches and intracellular survival involve ExoS ADP-r activity and implicate a connection between bleb niche formation and the known role(s) of ExoS-mediated apoptosis and/or Rab GTPase inactivation. ..
- Jeong B, Lin Y, Joe A, Guo M, Korneli C, Yang H, et al. Structure function analysis of an ADP-ribosyltransferase type III effector and its RNA-binding target in plant immunity. J Biol Chem. 2011;286:43272-81 pubmed publisher..These data provide mechanistic details how HopU1 recognizes this novel type of substrate and highlights the role of GRP7 in plant immunity. ..
- Jørgensen R, Wang Y, Visschedyk D, Merrill A. The nature and character of the transition state for the ADP-ribosyltransferase reaction. EMBO Rep. 2008;9:802-9 pubmed publisher..On the basis of these data, we propose a transition-state model for the toxin-catalysed reaction. ..