<scp>ADP</scp>‐ribosylation: new facets of an ancient modification

Palazzo, Luca; Mikoč, Andreja; Ahel, Ivan

doi:10.1111/febs.14078

Cited by 120 publications

(138 citation statements)

References 184 publications

(338 reference statements)

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“…ART enzymes are widely distributed across all domains of life from bacteria to humans with exception of yeasts [2,5,31,97] and, according to the structural organisation of the ART fold, are subdivided into diphtheria toxin-like (ARTDs) and cholera toxin-like ARTs (ARTCs) classes [42,45]. Despite low sequence similarity, the two classes of ART domains share a common conserved secondary structure and protein…”

Section: Adp-ribosyl Transferases (Arts)mentioning

confidence: 99%

“…ARTs are mainly known in modifying proteins, however, several enzymes can modify additional molecules, such as nucleic acids (both DNA and RNA) and antibiotics [5][6][7]34,78]. The structure of bARTs is overall conserved in eukaryotic homologues belonging to same families, however, the selectivity for targets is clearly divergent throughout the evolution.…”

Section: Substrates Of Adprmentioning

confidence: 99%

“…ADP-ribosylation (ADPr) is a reversible regulatory mechanism widespread in viruses, bacteria and in the large part of eukaryotes [1][2][3][4][5]. ADPr is catalysed by enzymes transferring ADP-ribose unit(s) from nicotinamide adenine dinucleotide (NAD + ) mainly onto cellular protein substrates with the release of nicotinamide [5]. However, additional cellular macromolecules, such as DNA and antibiotics, are target of ADPr [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Targeting ADP-ribosylation as an antimicrobial strategy

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Valente

et al. 2019

Biochemical Pharmacology

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A B S T R A C T ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.T large number of worldwide spread diseases, affecting humans, insects and plants [31,[56][57][58], with a great impact on human health. In addition, infectious diseases strongly affect the world economy in terms of costs for the human health as well as food and agricultural economic losses [59]. The use of antibiotics to counteract the pathogen infections has represented the therapeutic strategy of choice in the last century, however the emergence of antibiotic resistance strains represents the major challenge of the 21st century [60][61][62]. Targeting bacterial pathogenic mechanisms by disarming pathogens of virulence factors, for instance by inhibiting the enzymatic activity of bART, represents a valid alternative intervention strategy to overcome antibiotic resistance [63][64][65][66]. In addition, because of the conservation of ADPr systems throughout the evolution, the understanding of bacterial pathogenic mechanisms may contribute to unveil novel and conserved cellular processes regulated by ADPr in high organisms [34,45,67,68]. The dysregulation of such processes can be either cause of human diseases or be target of therapeutic intervention [39,[69][70][71].Herein, we will provide a summary of bacterial ADPr systems describing their pathogenic mechanisms and highlighting the similarities with ADPr systems in mammals as well. Further, we discuss the potential of targeting ADPr for therapeutic strategies of infection diseases. ADP-ribosylation in pathophysiologyADPr was originally described in the 60s; two independent studies reported the identification of a new polymer, poly(ADP-ribose) (PAR) synthesised from NAD + in vertebrate cells [72] and, simultaneously, the finding that bacterial DTX activity from C. diphteriae is dependent on NAD + content [73]. In the following decades, research in the field has expanded the involvement of ADPr ...

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Section: Adp-ribosyl Transferases (Arts)mentioning

confidence: 99%

Section: Substrates Of Adprmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting ADP-ribosylation as an antimicrobial strategy

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Valente

et al. 2019

Biochemical Pharmacology

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“…The most prominent role of nicotinamide adenine dinucleotide ( NAD + , Figure ) is as a redox cofactor in regulating central metabolic pathways by catalyzing a variety of oxidoreductase‐mediated processes . Moreover, NAD + has been recently found to act as a substrate for multiple enzymes that catalyze glycosidic cleavage of the nicotinamide moiety and release an ADP‐ribose ( ADPr ) moiety, which is then transferred onto acceptor molecules, such as proteins, DNA, and smaller metabolites …”

Section: Introductionmentioning

confidence: 99%

“…In this regard, three major classes of NAD + ‐consuming enzymes are commonly identified, including sirtuins, (ADP‐ribose)polymerases and cyclic ADP‐ribose synthases . Malfunction or dysregulation of these enzymes have been found to disrupt cellular NAD + homoeostasis and, as a consequence, could cause severe diseases, such as cancer, diabetics, atherosclerosis, Alzheimer's disease, depressions, and neurodegeneration …”

Section: Introductionmentioning

confidence: 99%

Emissive Synthetic Cofactors: A Highly Responsive NAD⁺Analogue Reveals Biomolecular Recognition Features

Feldmann

Tor

2019

Chemistry A European J

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Apart from its vital function as a redox cofactor, nicotinamide adenine dinucleotide (NAD+) has emerged as a crucial substrate for NAD+‐consuming enzymes, including poly(ADP‐ribosyl)transferase 1 (PARP1) and CD38/CD157. Their association with severe diseases, such as cancer, Alzheimer's disease, and depressions, necessitates the development of new analytical tools based on traceable NAD+ surrogates. Here, the synthesis, photophysics and biochemical utilization of an emissive, thieno[3,4‐d]pyrimidine‐based NAD+ surrogate, termed NthAD+, are described. Its preparation was accomplished by enzymatic conversion of synthetic thATP by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1). The new NAD+ analogue possesses useful photophysical features including redshifted absorption and emission maxima as well as a relatively high quantum yield. Serving as a versatile substrate, NthAD+ was reduced by alcohol dehydrogenase (ADH) to NthADH and afforded thADP‐ribose (thADPr) upon hydrolysis by NAD+‐nucleosidase (NADase). Furthermore, NthAD+ was engaged in cholera toxin A (CTA)‐catalyzed mono(thADP‐ribosyl)ation, but was found incapable in promoting PARP1‐mediated poly(thADP‐ribosyl)ation. Due to its high photophysical responsiveness, NthAD+ is suited for spectroscopic real‐time monitoring. Intriguingly, and as an N7‐lacking NAD+ surrogate, the thieno‐based cofactor showed reduced compatibility (i.e., functional similarity compared to native NAD+) relative to its isothiazolo‐based analogue. The distinct tolerance, displayed by diverse NAD+ producing and consuming enzymes, suggests unique biological recognition features and dependency on the purine N7 moiety, which is found to be of importance, if not essential, for PARP1‐mediated reactions.

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Uncommon posttranslational modifications in proteomics: ADP‐ribosylation, tyrosine nitration, and tyrosine sulfation

Bashyal

Brodbelt

2022

Mass Spectrometry Reviews

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Posttranslational modifications (PTMs) are covalent modifications of proteins that modulate the structure and functions of proteins and regulate biological processes. The development of various mass spectrometry‐based proteomics workflows has facilitated the identification of hundreds of PTMs and aided the understanding of biological significance in a high throughput manner. Improvements in sample preparation and PTM enrichment techniques, instrumentation for liquid chromatography‐tandem mass spectrometry (LC‐MS/MS), and advanced data analysis tools enhance the specificity and sensitivity of PTM identification. Highly prevalent PTMs like phosphorylation, glycosylation, acetylation, ubiquitinylation, and methylation are extensively studied. However, the functions and impact of less abundant PTMs are not as well understood and underscore the need for analytical methods that aim to characterize these PTMs. This review focuses on the advancement and analytical challenges associated with the characterization of three less common but biologically relevant PTMs, specifically, adenosine diphosphate‐ribosylation, tyrosine sulfation, and tyrosine nitration. The advantages and disadvantages of various enrichment, separation, and MS/MS techniques utilized to identify and localize these PTMs are described.

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ADP‐ribosylation: new facets of an ancient modification

Cited by 120 publications

References 184 publications

Targeting ADP-ribosylation as an antimicrobial strategy

Targeting ADP-ribosylation as an antimicrobial strategy

Emissive Synthetic Cofactors: A Highly Responsive NAD⁺Analogue Reveals Biomolecular Recognition Features

Uncommon posttranslational modifications in proteomics: ADP‐ribosylation, tyrosine nitration, and tyrosine sulfation

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ADP‐ribosylation: new facets of an ancient modification

Cited by 120 publications

References 184 publications

Targeting ADP-ribosylation as an antimicrobial strategy

Targeting ADP-ribosylation as an antimicrobial strategy

Emissive Synthetic Cofactors: A Highly Responsive NAD+Analogue Reveals Biomolecular Recognition Features

Uncommon posttranslational modifications in proteomics: ADP‐ribosylation, tyrosine nitration, and tyrosine sulfation

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Emissive Synthetic Cofactors: A Highly Responsive NAD⁺Analogue Reveals Biomolecular Recognition Features