Academic literature on the topic 'Macrodomains'

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Journal articles on the topic "Macrodomains"

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Delgado-Rodriguez, Sofia E., Andrew P. Ryan, and Matthew D. Daugherty. "Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins." Pathogens 12, no. 5 (2023): 674. http://dx.doi.org/10.3390/pathogens12050674.

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Protein post-translational modifications (PTMs) are an important battleground in the evolutionary arms races that are waged between the host innate immune system and viruses. One such PTM, ADP-ribosylation, has recently emerged as an important mediator of host antiviral immunity. Important for the host–virus conflict over this PTM is the addition of ADP-ribose by PARP proteins and removal of ADP-ribose by macrodomain-containing proteins. Interestingly, several host proteins, known as macroPARPs, contain macrodomains as well as a PARP domain, and these proteins are both important for the host a
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Haikarainen, Teemu, Mirko M. Maksimainen, Ezeogo Obaji, and Lari Lehtiö. "Development of an Inhibitor Screening Assay for Mono-ADP-Ribosyl Hydrolyzing Macrodomains Using AlphaScreen Technology." SLAS DISCOVERY: Advancing the Science of Drug Discovery 23, no. 3 (2017): 255–63. http://dx.doi.org/10.1177/2472555217737006.

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Protein mono-ADP-ribosylation is a posttranslational modification involved in the regulation of several cellular signaling pathways. Cellular ADP-ribosylation is regulated by ADP-ribose hydrolases via a hydrolysis of the protein-linked ADP-ribose. Most of the ADP-ribose hydrolases share a macrodomain fold. Macrodomains have been linked to several diseases, such as cancer, but their cellular roles are mostly unknown. Currently, there are no inhibitors available targeting the mono-ADP-ribose hydrolyzing macrodomains. We have developed a robust AlphaScreen assay for the screening of inhibitors ag
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Hammond, Robert G., Norbert Schormann, Robert Lyle McPherson, Anthony K. L. Leung, Champion C. S. Deivanayagam, and Margaret A. Johnson. "ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4." Proceedings of the National Academy of Sciences 118, no. 2 (2021): e2004500118. http://dx.doi.org/10.1073/pnas.2004500118.

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Macrodomains are proteins that recognize and hydrolyze ADP ribose (ADPR) modifications of intracellular proteins. Macrodomains are implicated in viral genome replication and interference with host cell immune responses. They are important to the infectious cycle of Coronaviridae and Togaviridae viruses. We describe crystal structures of the conserved macrodomain from the bat coronavirus (CoV) HKU4 in complex with ligands. The structures reveal a binding cavity that accommodates ADPR and analogs via local structural changes within the pocket. Using a radioactive assay, we present evidence of mo
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Rack, Johannes Gregor Matthias, Valentina Zorzini, Zihan Zhu, Marion Schuller, Dragana Ahel, and Ivan Ahel. "Viral macrodomains: a structural and evolutionary assessment of the pharmacological potential." Open Biology 10, no. 11 (2020): 200237. http://dx.doi.org/10.1098/rsob.200237.

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Viral macrodomains possess the ability to counteract host ADP-ribosylation, a post-translational modification implicated in the creation of an antiviral environment via immune response regulation. This brought them into focus as promising therapeutic targets, albeit the close homology to some of the human macrodomains raised concerns regarding potential cross-reactivity and adverse effects for the host. Here, we evaluate the structure and function of the macrodomain of SARS-CoV-2, the causative agent of COVID-19. We show that it can antagonize ADP-ribosylation by PARP14, a cellular (ADP-ribosy
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Ekblad, Torun, Patricia Verheugd, Anders E. Lindgren, Tomas Nyman, Mikael Elofsson, and Herwig Schüler. "Identification of Poly(ADP-Ribose) Polymerase Macrodomain Inhibitors Using an AlphaScreen Protocol." SLAS DISCOVERY: Advancing the Science of Drug Discovery 23, no. 4 (2018): 353–62. http://dx.doi.org/10.1177/2472555217750870.

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Macrodomains recognize intracellular adenosine diphosphate (ADP)-ribosylation resulting in either removal of the modification or a protein interaction event. Research into compounds that modulate macrodomain functions could make important contributions. We investigated the interactions of all seven individual macrodomains of the human poly(ADP-ribose) polymerase (PARP) family members PARP9, PARP14, and PARP15 with five mono-ADP-ribosylated (automodified) ADP-ribosyltransferase domains using an AlphaScreen assay. Several mono-ADP-ribosylation-dependent interactions were identified, and they wer
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Kuri, Thomas, Klara K. Eriksson, Akos Putics, et al. "The ADP-ribose-1″-monophosphatase domains of severe acute respiratory syndrome coronavirus and human coronavirus 229E mediate resistance to antiviral interferon responses." Journal of General Virology 92, no. 8 (2011): 1899–905. http://dx.doi.org/10.1099/vir.0.031856-0.

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Several plus-strand RNA viruses encode proteins containing macrodomains. These domains possess ADP-ribose-1″-phosphatase (ADRP) activity and/or bind poly(ADP-ribose), poly(A) or poly(G). The relevance of these activities in the viral life cycle has not yet been resolved. Here, we report that genetically engineered mutants of severe acute respiratory syndrome coronavirus (SARS-CoV) and human coronavirus 229E (HCoV-229E) expressing ADRP-deficient macrodomains displayed an increased sensitivity to the antiviral effect of alpha interferon compared with their wild-type counterparts. The data sugges
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Hussain, Irfan, Nashaiman Pervaiz, Abbas Khan, et al. "Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity." Genes & Immunity 21, no. 6-8 (2020): 409–19. http://dx.doi.org/10.1038/s41435-020-00120-6.

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AbstractThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3). However, no substantial information is available concerning the relationship of macrodomains to the unusually high pathogeni
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Leung, Anthony K. L., Diane E. Griffin, Jürgen Bosch, and Anthony R. Fehr. "The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses." Pathogens 11, no. 1 (2022): 94. http://dx.doi.org/10.3390/pathogens11010094.

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Emerging and re-emerging viral diseases pose continuous public health threats, and effective control requires a combination of non-pharmacologic interventions, treatment with antivirals, and prevention with vaccines. The COVID-19 pandemic has demonstrated that the world was least prepared to provide effective treatments. This lack of preparedness has been due, in large part, to a lack of investment in developing a diverse portfolio of antiviral agents, particularly those ready to combat viruses of pandemic potential. Here, we focus on a drug target called macrodomain that is critical for the r
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Zapata-Pérez, Rubén, Fernando Gil-Ortiz, Ana Belén Martínez-Moñino, Antonio Ginés García-Saura, Jordi Juanhuix, and Álvaro Sánchez-Ferrer. "Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis." Open Biology 7, no. 4 (2017): 160327. http://dx.doi.org/10.1098/rsob.160327.

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Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely ha
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Alhammad, Yousef M. O., and Anthony R. Fehr. "The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation." Viruses 12, no. 4 (2020): 384. http://dx.doi.org/10.3390/v12040384.

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Macrodomains, enzymes that remove ADP-ribose from proteins, are encoded by several families of RNA viruses and have recently been shown to counter innate immune responses to virus infection. ADP-ribose is covalently attached to target proteins by poly-ADP-ribose polymerases (PARPs), using nicotinamide adenine dinucleotide (NAD+) as a substrate. This modification can have a wide variety of effects on proteins including alteration of enzyme activity, protein–protein interactions, and protein stability. Several PARPs are induced by interferon (IFN) and are known to have antiviral properties, impl
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Dissertations / Theses on the topic "Macrodomains"

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Russo, Alessandra. "Design, synthesis and biological activity of new target selective antitumoral agents." Doctoral thesis, Universita degli studi di Salerno, 2018. http://hdl.handle.net/10556/3037.

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2016 - 2017<br>Cancer development is a complex pathological process that exploits a variety of biological actors. The identification of new molecular entities able to interfere with new biological targets, involved in tumorigenesis, is strongly needed, both for the development of new promising drug candidates, and, as chemical probes useful to further investigate less understood biological aspects. Two main targets, involved at different levels, in cancer development, have been thoroughly investigated: Macrodomain proteins, MacroD1 and MacroD2, and the Bcl-2 associated athanogene 3, BAG3 prote
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Forst, Alexandra [Verfasser]. "Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains and acetylation of ARTD10 / Alexandra Forst." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/105148779X/34.

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Thiel, Axel. "Organisation du chromosome d' Escherichia coli en macrodomaines et régions non-structurées." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112143.

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Le chromosome circulaire de la bactérie Escherichia coli est composé de quatre macrodomaines et deux régions non structurées. Cette organisation influence la ségrégation des chromatides sœurs et la mobilité de l’ADN chromosomique. La structuration de la région terminus (Ter) en macrodomaine est lié à l’interaction de la protéine MatP avec la séquence cible de 13 pb (sic) appelée matS répétée 23 fois dans ce domaine de 800 kb. Le travail réalisé durant ma thèse a permis l’identification et la caractérisation d’un système site-spécifique qui restreint à la région Ter un effet associé à la protéi
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Schuller, Marion. "Investigating strategies to modify PARP14 function through macrodomain inhibition." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:51a76ee9-609a-4765-ab55-d95a64e2bb7d.

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Macrodomains are conserved protein interaction modules that are present in all domains of life and mediate recognition of sequence motifs harbouring adenosine diphosphate ribose (ADPR) modifications. In addition, some of them are able to control the turnover of ADPR signalling through their catalytic activity removing these modifications. Macrodomains are hence implicated in a variety of cellular processes as well as in diseases including cancer and viral pathogenesis. The polyadenosine-diphosphate-ribose polymerase (PARP) family member PARP14 is one of twelve human macrodomain-containing prot
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Mercier, Romain. "Organisation du chromosome d'Escherichia coli en macrodomaines : identification et rôle du système spécifique de site matS-MatP." Paris 11, 2009. http://www.theses.fr/2009PA112361.

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Le génome d’E. Coli est composé d’un chromosome unique et circulaire d’une taille de 4,6Mb. Le chromosome est organisé selon différentes échelles : (i) nucléotidique par les séquences codantes et les motifs d’ADN fonctionnels ; (ii) locale par les domains topologiques ou plectonèmes ; (iii) globale par les réplichores et les macrodomaines. Mon travail de thèse s’est attaché à l’étude de l’organisation globale du chromosome en macrodomaines. Le chromosome d’E. Coli est composé de quatre macrodomaines et de deux régions Non‐Struturées. Les macrodomaines divisent le chromosome en quatre unités st
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Smith, Alexandra Kimberly. "A Mutational-Functional Analysis of the Escherichia coli Macrodomain Protein, YmdB." Thesis, Temple University, 2019. http://pqdtopen.proquest.com/#viewpdf?dispub=10933701.

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<p> Gene expression pathways exhibit many "twists and turns," with theoretically numerous ways in which the pathways can be regulated by both negative and positive feedback mechanisms. A key step in gene expression is RNA maturation (RNA processing), which in the bacterial cell can be accomplished through RNA binding and enzymatic cleavages. The well-characterized bacterial protein Ribonuclease III (RNase III), is a conserved, double-stranded(ds)-specific ribonuclease. In the gram-negative bacterium <i>Escherichia coli</i>, RNase III catalytic activity is subject to both positive and negative
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Smith, Alexandra Kimberly. "A MUTATIONAL-FUNCTIONAL ANALYSIS OF THE ESCHERICHIA COLI MACRODOMAIN PROTEIN, YMDB." Master's thesis, Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/539353.

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Biology<br>M.S.<br>Gene expression pathways exhibit many “twists and turns,” with theoretically numerous ways in which the pathways can be regulated by both negative and positive feedback mechanisms. A key step in gene expression is RNA maturation (RNA processing), which in the bacterial cell can be accomplished through RNA binding and enzymatic cleavages. The well-characterized bacterial protein Ribonuclease III (RNase III), is a conserved, double-stranded(ds)-specific ribonuclease. In the gram-negative bacterium Escherichia coli, RNase III catalytic activity is subject to both positive and n
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Esnault, Emilie. "Etude de la conformation du chromosome chez la bactérie escherichia coli : plasticité et contraintes." Paris 11, 2008. http://www.theses.fr/2008PA112144.

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La connaissance des paramètres contraignant l'organisation des chromosomes est importante pour la compréhension plus générale du fonctionnement de la cellule. La plupart des génomes bactériens sont circulaires. Leur réplication progresse de façon bidirectionnelle à partir d'une origine unique et se termine dans la région opposée. La conformation chromosomique naturelle a été modifiée par des inversions. L'impact de ces réarrangements sur la physiologie de la cellule a été regardé. Les résultats montrent que le positionnement préférentiel des gènes sur le brin direct, la localisation des gènes
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Paudyal, Samridhdi. "FUNCTIONAL ANALYSIS OF THE BACTERIAL MACRODOMAIN PROTEIN YMDB AND ITS INTERACTION WITH RIBONUCLEASE III." Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/271085.

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Biology<br>Ph.D.<br>The Escherichia coli ymdB gene encodes a ~19 kDa protein that binds ADP-ribose (ADPR) and metabolites related to NAD+. As such, it has been termed a macrodomain protein, referring to a conserved fold that binds ADPR. YmdB can catalyze the hydrolysis of O-acetyl-ADP-ribose (OAADPR), forming acetate and ADPR. OAADPR is a product of sirtuin action on lysine-acetylated proteins, which involves NAD+ as a cosubstrate. There is evidence that YmdB interacts with other proteins, including the conserved enzyme, ribonuclease III. Ribonuclease III (RNase III) is a double-strand(ds)-spe
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Lesterlin, Christian. "Rôles de l'organisation en réplichores et en macrodomaines dans la ségrégation du chromosome d'Escherichia coli." Toulouse 3, 2005. http://www.theses.fr/2005TOU30119.

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Le génome d'E. Coli est composé d'une molécule d'ADN circulaire de 4,6 Mb, qui, in vivo, est compactée en une structure organisée appelée nucléoïde, qui s'organise selon deux modes, en macrodomaines et en réplichores. Les macrodomaines sont de grandes régions chromosomiques composées de séquences qui montrent la même localisation intracellulaire moyenne au cours du cycle et capables d'entrer en contact entre elles. Les réplichores sont définis comme les bras chromosomiques portant des biais de composition en bases sur toute leur longueur, ils coïncident avec les bras de réplication. Mes travau
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Book chapters on the topic "Macrodomains"

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Posavec Marjanovic´, Melanija, Gytis Jankevicius, and Ivan Ahel. "Hydrolysis of ADP-Ribosylation by Macrodomains." In Methods in Molecular Biology. Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8588-3_14.

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Garab, Gyozo. "Chirally Organized Macrodomains in Thylakoid Membranes. Possible Structural and Regulatory Roles." In Light as an Energy Source and Information Carrier in Plant Physiology. Springer US, 1996. http://dx.doi.org/10.1007/978-1-4613-0409-8_10.

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Smith, Rebecca, and Gyula Timinszky. "Monitoring Poly(ADP-Ribosyl)ation in Response to DNA Damage in Live Cells Using Fluorescently Tagged Macrodomains." In Methods in Molecular Biology. Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8588-3_2.

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Bütepage, Mareike, Sarah Krieg, Laura Eckei, et al. "Assessment of Intracellular Auto-Modification Levels of ARTD10 Using Mono-ADP-Ribose-Specific Macrodomains 2 and 3 of Murine Artd8." In Methods in Molecular Biology. Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8588-3_4.

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Kamata, Teddy, Chun-Song Yang, Kasey Jividen, et al. "Detection of ADP-Ribosylation of the Androgen Receptor Using the Recombinant Macrodomain AF1521 from Archaeoglobus fulgidus." In Methods in Molecular Biology. Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9195-2_9.

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Conference papers on the topic "Macrodomains"

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Whaley, Paul W. "A Probabilistic Model for Inelastic Deformation." In ASME 1996 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1996. http://dx.doi.org/10.1115/imece1996-0581.

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Abstract A probabilistic model for inelastic deformation is described based on three scale domains to relate properties of the crystalline structure to mechanical response. The microdomain is the scale of the grain structure. Each microelement is composed of a strain-rate sensitive element, a strain-hardening element and a plastic slip element with the yield point modeled as a random variable. The mesodomain is the population of microelements, and the macrodomain is the scale of expected value calculations. The Rayleigh probability distribution function was used to model random yielding in a n
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Antypenko, Lyudmyla, Oleksii Antypenko, and Sergiy Kovalenko. "MOLECULAR DOCKING OF [1,2,4]TRIAZOLO [1,5-c]QUINAZOLINES TO SARS-CoV-2 NON-STRUCTURAL PROTEIN 3 MACRODOMAIN (6YWM)." In RICERCHE SCIENTIFICHE E METODI DELLA LORO REALIZZAZIONE: ESPERIENZA MONDIALE E REALTÀ DOMESTICHE. European Scientific Platform, 2021. http://dx.doi.org/10.36074/logos-26.11.2021.v3.41.

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Reports on the topic "Macrodomains"

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ASAP - SARS-CoV-2 nsp3 macrodomain single point. EMBL-EBI, 2024. https://doi.org/10.6019/chembl5442379.

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ASAP - SARS-CoV-2 nsp3 macrodomain dose response. EMBL-EBI, 2024. https://doi.org/10.6019/chembl5441456.

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