Scabin, a Novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies

Lyons, Bronwyn; Ravulapalli, R.; Lanoue, Jason; Lugo, Miguel R.; Dutta, Debajyoti; Carlin, Stephanie; Merrill, A. Rod

doi:10.1074/jbc.m115.707653

Cited by 47 publications

(74 citation statements)

References 45 publications

(58 reference statements)

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“…Two ARTs have been characterized in Streptomyces , SCO5461 from Str. coelicolor and Scabin from plant pathogen Streptomyces scabies . These proteins are homologues of pierisins and possess guanine‐specific DNA ART activity, but they are not conserved across the Streptomyces species and cannot be found in Str.…”

Section: Adp‐ribosylation In Bacteriamentioning

confidence: 99%

ADP‐ribosylation: new facets of an ancient modification

2017

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Rapid response to environmental changes is achieved by uni‐ and multicellular organisms through a series of molecular events, often involving modification of macromolecules, including proteins, nucleic acids and lipids. Amongst these, ADP‐ribosylation is of emerging interest because of its ability to modify different macromolecules in the cells, and its association with many key biological processes, such as DNA‐damage repair, DNA replication, transcription, cell division, signal transduction, stress and infection responses, microbial pathogenicity and aging. In this review, we provide an update on novel pathways and mechanisms regulated by ADP‐ribosylation in organisms coming from all kingdoms of life.

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Section: Adp‐ribosylation In Bacteriamentioning

confidence: 99%

ADP‐ribosylation: new facets of an ancient modification

2017

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“…The bacterial ADP-ribosyltransferase (bART) toxins are a large family of potentially lethal intracellular toxins. Members of this toxin family covalently add ADP-ribose to intracellular target proteins and DNA, thereby modifying or inhibiting normal macromolecule function (Holbourn et al, 2006;Yates et al, 2006;Lyons et al, 2016). Most of the target proteins such as Rho proteins, heterotrimeric G-proteins or actin, are key regulators of cellular functions (Aktories et al, 2000;Simon et al, 2014;Aktories, 2015).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the toxin Plx2A, a RhoA‐targeting ADP‐ribosyltransferase produced by the honey bee pathogen Paenibacillus larvae

Ebeling

Fünfhaus

Knispel

et al. 2017

Environmental Microbiology

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The toxin Plx2A is an important virulence factor of Paenibacillus larvae, the etiological agent of American Foulbrood, the most destructive bacterial disease of honey bees. Biochemical and functional analyses as well as the crystal structure of Plx2A revealed that it belongs to the C3 mono-ADP-ribosylating toxin subgroup. RhoA was identified as the cellular target of Plx2A activity. The kinetic parameters (K , k ) were established for both the transferase and glycohydrolase reactions. When expressed in yeast, Plx2A was cytotoxic for eukaryotic cells and catalytic variants confirmed that the cytotoxicity of Plx2A depends on its enzymatic activity. The crystal structure of Plx2A was solved to 1.65 Å and confirmed that it is a C3-like toxin, although with a new molecular twist, it has a B-domain. A molecular model of the 'active' enzyme conformation in complex with NAD was produced by computational methods based on the recent structure of C3bot1 with RhoA. In murine macrophages, Plx2A induced actin cytoskeleton reorganization while in insect cells, vacuolization and the occurrence of bi-nucleated cells was observed. The latter is indicative of an inhibition of cytokinesis. All these cellular effects are consistent with Plx2A inhibiting the activity of RhoA by covalent modification.

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“…Enzymatically active ARTs utilize a protein fold called the ART fold to catalyze these linkages at the 1″ position of the nicotinamide ribose via an SN 1 -like reaction mechanism2. Although most ARTs modify proteins (specifically at nucleophilic amino acids) some modify other substrate molecules, including tRNAs 3,4 polynucleic acids 5–9 , and small-molecule antimicrobials 10,11 . ADP-ribosylation of target proteins by ARTs plays important functions in cells.…”

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confidence: 99%

Insights into the biogenesis, function, and regulation of ADP-ribosylation

2018

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ADP-ribosylation—the transfer of ADP-ribose (ADPr) from NAD+ onto target molecules—is catalyzed by members of the ADP-ribosyltransferase (ART) superfamily of proteins, found in all kingdoms of life. Modification of amino acids in protein targets by ADPr regulates critical cellular pathways in eukaryotes and underlies the pathogenicity of certain bacteria. Several members of the ART superfamily are highly relevant for disease; these include the poly(ADP-ribose) polymerases (PARPs), recently shown to be important cancer targets, and the bacterial toxins diphtheria toxin and cholera toxin, long known to be responsible for the symptoms of diphtheria and cholera that result in morbidity. In this Review, we discuss the functions of amino acid ADPr modifications and the ART proteins that make them, the nature of the chemical linkage between ADPr and its targets and how this impacts function and stability, and the way that ARTs select specific amino acids in targets to modify.

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Scabin, a Novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies

Cited by 47 publications

References 45 publications

ADP‐ribosylation: new facets of an ancient modification

ADP‐ribosylation: new facets of an ancient modification

Characterization of the toxin Plx2A, a RhoA‐targeting ADP‐ribosyltransferase produced by the honey bee pathogen Paenibacillus larvae

Insights into the biogenesis, function, and regulation of ADP-ribosylation

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