LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 198

Search options

  1. Book ; Online: Radiation-induced and oxidative DNA damages

    Dumont, Elise / Chatgilialoglu, Chryssostomos / Monari, Antonio

    2015  

    Abstract: DNA stores and passes the genetic information of almost all living organisms. Its molecular structure and their intramolecular interactions are particularly suitable to maximize stability against oxidative stress and UV-light absorption. Yet the ... ...

    Abstract DNA stores and passes the genetic information of almost all living organisms. Its molecular structure and their intramolecular interactions are particularly suitable to maximize stability against oxidative stress and UV-light absorption. Yet the protection and repair strategies are still error-prone: DNA lesions are produced, including the most complex and highly mutagenic ones. An important threat to DNA stability comes from photosensitization, i.e. from the dramatic multiplication of radiation-induced defects mediated by the presence of organic or organometallic dyes compared to the direct exposure to UVA radiation. Moreover, the photo-induced production of singlet oxygen generates an extremely high oxidative stress on DNA that, in vivo, normally results in extended cellular apoptosis.-

    Elucidating the processes leading to DNA damages, from the production of a simple radical entity to deleterious lesions, as well as the opportunities of repair by devoted enzymes, is a cornerstone towards the development of more efficient protection strategies. Sensitization and selective production of DNA lesions can also be exploited to induce the selective apoptosis of cancer cells upon exposition to radiation or to oxidative stress, for instance in the field of photodynamic therapy. The importance and relevance of the field is witnessed by the impressive amount of high-level papers dealing with this complex subject, and notably tackling the structural elucidation of DNA and DNA-drug adducts, the mechanisms of formation of DNA lesions (including the precise detection of the final lesion products), as well as the influence of the lesions on the DNA stability and dynamics and the consequences on the ease of repair.-

    Due to the complexity of the field lying at the frontiers between chemistry, physics and biology, multidisciplinary strategies allying modeling and experience are needed. This topic aims at giving an extended overview of the current research in the domain, with fundamental contribution from the leading groups in the field of DNA reactivity, structural characterization, photo-chemistry and photo-physics, as well as repair mechanism. It will therefore be a fundamental guide for scientists wanting to address the field of DNA lesion and repair, but also more generally for researchers working in rational drug design or in the development of biomarkers and medical imaging techniques
    Keywords Science (General) ; Chemistry
    Size 1 electronic resource (93 p.)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT020091848
    ISBN 9782889196609 ; 2889196607
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

    More links

    Kategorien

  2. Article ; Online: Interaction of the Immune System TIM-3 Protein with a Model Cellular Membrane Containing Phosphatidyl-Serine Lipids.

    Delova, Anastasiia / Pasc, Andreea / Monari, Antonio

    Chemistry (Weinheim an der Bergstrasse, Germany)

    2024  Volume 30, Issue 22, Page(s) e202304318

    Abstract: T cell transmembrane, Immunoglobulin, and Mucin (TIM) are important immune system proteins which are especially present in T-cells and regulated the immune system by sensing cell engulfment and apoptotic processes. Their role is exerted by the capacity ... ...

    Abstract T cell transmembrane, Immunoglobulin, and Mucin (TIM) are important immune system proteins which are especially present in T-cells and regulated the immune system by sensing cell engulfment and apoptotic processes. Their role is exerted by the capacity to detect the presence of phosphatidyl-serine lipid polar head in the outer leaflet of cellular membranes (correlated with apoptosis). In this contribution by using equilibrium and enhanced sampling molecular dynamics simulation we unravel the molecular bases and the thermodynamics of TIM, and in particular TIM-3, interaction with phosphatidyl serine in a lipid bilayer. Since TIM-3 deregulation is an important factor of pro-oncogenic tumor micro-environment understanding its functioning at a molecular level may pave the way to the development of original immunotherapeutic approaches.
    MeSH term(s) Hepatitis A Virus Cellular Receptor 2 ; Membrane Proteins/metabolism ; Mucin-3 ; Phosphatidylserines ; Membrane Lipids ; T-Lymphocytes ; Mucins ; Serine
    Chemical Substances Hepatitis A Virus Cellular Receptor 2 ; Membrane Proteins ; Mucin-3 ; Phosphatidylserines ; Membrane Lipids ; Mucins ; Serine (452VLY9402)
    Language English
    Publishing date 2024-02-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1478547-X
    ISSN 1521-3765 ; 0947-6539
    ISSN (online) 1521-3765
    ISSN 0947-6539
    DOI 10.1002/chem.202304318
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: A Portrait of the Chromophore as a Young System-Quantum-Derived Force Field Unraveling Solvent Reorganization upon Optical Excitation of Cyclocurcumin Derivatives.

    Losantos, Raúl / Prampolini, Giacomo / Monari, Antonio

    Molecules (Basel, Switzerland)

    2024  Volume 29, Issue 8

    Abstract: The study of fast non-equilibrium solvent relaxation in organic chromophores is still challenging for molecular modeling and simulation approaches, and is often overlooked, even in the case of non-adiabatic dynamics simulations. Yet, especially in the ... ...

    Abstract The study of fast non-equilibrium solvent relaxation in organic chromophores is still challenging for molecular modeling and simulation approaches, and is often overlooked, even in the case of non-adiabatic dynamics simulations. Yet, especially in the case of photoswitches, the interaction with the environment can strongly modulate the photophysical outcomes. To unravel such a delicate interplay, in the present contribution we resorted to a mixed quantum-classical approach, based on quantum mechanically derived force fields. The main task is to rationalize the solvent reorganization pathways in chromophores derived from cyclocurcumin, which are suitable for light-activated chemotherapy to destabilize cellular lipid membranes. The accurate and reliable decryption delivered by the quantum-derived force fields points to important differences in the solvent's reorganization, in terms of both structure and time scale evolution.
    Language English
    Publishing date 2024-04-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules29081752
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Interaction between

    Vasseur, Laurine / Barbault, Florent / Monari, Antonio

    The journal of physical chemistry. B

    2024  Volume 128, Issue 16, Page(s) 3929–3936

    Abstract: ... Yersinia ... ...

    Abstract Yersinia pestis
    MeSH term(s) Vitronectin/chemistry ; Vitronectin/metabolism ; Bacterial Outer Membrane Proteins/chemistry ; Bacterial Outer Membrane Proteins/metabolism ; Humans ; Molecular Dynamics Simulation ; Yersinia pestis/chemistry ; Yersinia pestis/metabolism ; Virulence Factors/chemistry ; Virulence Factors/metabolism ; Protein Domains ; Protein Binding
    Chemical Substances Vitronectin ; Bacterial Outer Membrane Proteins ; Ail protein, Yersinia pestis ; Virulence Factors
    Language English
    Publishing date 2024-04-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1520-5207
    ISSN (online) 1520-5207
    DOI 10.1021/acs.jpcb.4c00965
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Modeling the Enzymatic Mechanism of the SARS-CoV-2 RNA-Dependent RNA Polymerase by DFT/MM-MD: An Unusual Active Site Leading to High Replication Rates.

    Bignon, Emmanuelle / Monari, Antonio

    Journal of chemical information and modeling

    2022  Volume 62, Issue 17, Page(s) 4261–4269

    Abstract: Viral infection relies on the hijacking of cellular machineries to enforce the reproduction of the infecting virus and its subsequent diffusion. In this context, the replication of the viral genome is a key step performed by specific enzymes, i.e., ... ...

    Abstract Viral infection relies on the hijacking of cellular machineries to enforce the reproduction of the infecting virus and its subsequent diffusion. In this context, the replication of the viral genome is a key step performed by specific enzymes, i.e., polymerases. The replication of SARS-CoV-2, the causative agent of the COVID-19 pandemics, is based on the duplication of its RNA genome, an action performed by the viral RNA-dependent RNA polymerase. In this contribution, by using highly demanding DFT/MM-MD computations coupled to 2D-umbrella sampling techniques, we have determined the chemical mechanisms leading to the inclusion of a nucleotide in the nascent viral RNA strand. These results highlight the high efficiency of the polymerase, which lowers the activation free energy to less than 10 kcal/mol. Furthermore, the SARS-CoV-2 polymerase active site is slightly different from those usually found in other similar enzymes, and in particular, it lacks the possibility to enforce a proton shuttle via a nearby histidine. Our simulations show that this absence is partially compensated by lysine whose proton assists the reaction, opening up an alternative, but highly efficient, reactive channel. Our results present the first mechanistic resolution of SARS-CoV-2 genome replication at the DFT/MM-MD level and shed light on its unusual enzymatic reactivity paving the way for the future rational design of antivirals targeting emerging RNA viruses.
    MeSH term(s) Antiviral Agents/pharmacology ; COVID-19 ; Catalytic Domain ; Humans ; Protons ; RNA, Viral/genetics ; RNA-Dependent RNA Polymerase ; SARS-CoV-2 ; Virus Replication
    Chemical Substances Antiviral Agents ; Protons ; RNA, Viral ; RNA-Dependent RNA Polymerase (EC 2.7.7.48)
    Language English
    Publishing date 2022-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 190019-5
    ISSN 1549-960X ; 0095-2338
    ISSN (online) 1549-960X
    ISSN 0095-2338
    DOI 10.1021/acs.jcim.2c00802
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Rationalizing the environment-dependent photophysical behavior of a DNA luminescent probe by classical and non-adiabatic molecular dynamics simulations.

    Monari, Antonio / Burger, Alain / Dumont, Elise

    Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology

    2023  Volume 22, Issue 9, Page(s) 2081–2092

    Abstract: Environment-sensitive fluorescent nucleoside analogs are of utmost importance to investigate the structure of nucleic acids, their intrinsic flexibility, and sequence-specific DNA- and RNA-binding proteins. The latter play indeed a key role in ... ...

    Abstract Environment-sensitive fluorescent nucleoside analogs are of utmost importance to investigate the structure of nucleic acids, their intrinsic flexibility, and sequence-specific DNA- and RNA-binding proteins. The latter play indeed a key role in transcription, translation as well as in the regulation of RNA stability, localization and turnover, and many other cellular processes. The sensitivity of the embedded fluorophore to polarity, hydration, and base stacking is clearly dependent on the specific excited-state relaxation mechanism and can be rationalized combining experimental and computational techniques. In this work, we elucidate the mechanisms leading to the population of the triplet state manifold for a versatile nucleobase surrogate, namely the 2-thienyl-3-hydroxychromone in gas phase, owing to non-adiabatic molecular dynamics simulations. Furthermore, we analyze its behavior in the B-DNA environment via classical molecular dynamics simulations, which evidence a rapid extrusion of the adenine facing the 2-thienyl-3-hydroxychromone nucleobase surrogate. Our simulations provide new insights into the dynamics of this family of chromophores, which could give rise to an integrated view and a fine tuning of their photochemistry, and namely the role of excited-state intramolecular proton transfer for the rational design of the next generation of fluorescent nucleoside analogs.
    MeSH term(s) Molecular Dynamics Simulation ; Nucleosides/chemistry ; DNA/chemistry ; Nucleic Acids ; Protons ; DNA Probes
    Chemical Substances Nucleosides ; DNA (9007-49-2) ; Nucleic Acids ; Protons ; DNA Probes
    Language English
    Publishing date 2023-05-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2072584-X
    ISSN 1474-9092 ; 1474-905X
    ISSN (online) 1474-9092
    ISSN 1474-905X
    DOI 10.1007/s43630-023-00431-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: How SARS-CoV-2 Alters the Regulation of Gene Expression in Infected Cells.

    Bignon, Emmanuelle / Grandemange, Stéphanie / Dumont, Elise / Monari, Antonio

    The journal of physical chemistry letters

    2023  Volume 14, Issue 13, Page(s) 3199–3207

    Abstract: Nonstructural accessory proteins in viruses play a key role in hijacking the basic cellular mechanisms, which is essential to promote the virus survival and evasion of the immune system. The immonuglobulin-like open reading frame 8 (ORF8) protein ... ...

    Abstract Nonstructural accessory proteins in viruses play a key role in hijacking the basic cellular mechanisms, which is essential to promote the virus survival and evasion of the immune system. The immonuglobulin-like open reading frame 8 (ORF8) protein expressed by SARS-CoV-2 accumulates in the nucleus and may influence the regulation of the gene expression in infected cells. In this contribution, by using microsecond time-scale all-atom molecular dynamics simulations, we unravel the structural bases behind the epigenetic action of ORF8. In particular, we highlight how the protein is able to form stable aggregates with DNA through a histone tail-like motif, and how this interaction is influenced by post-translational modifications, such as acetylation and methylation, which are known epigenetic markers in histones. Our work not only clarifies the molecular mechanisms behind the perturbation of the epigenetic regulation caused by the viral infection but also offers an unusual perspective which may foster the development of original antivirals.
    MeSH term(s) Humans ; SARS-CoV-2/metabolism ; Epigenesis, Genetic ; COVID-19/genetics ; Histones/metabolism ; Methylation
    Chemical Substances Histones
    Language English
    Publishing date 2023-03-27
    Publishing country United States
    Document type Journal Article
    ISSN 1948-7185
    ISSN (online) 1948-7185
    DOI 10.1021/acs.jpclett.3c00582
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Molecular Photoswitches Regulating the Activity of the Human Serotonin Transporter.

    Singer, Nadja K / González, Leticia / Monari, Antonio

    The journal of physical chemistry letters

    2023  Volume 14, Issue 46, Page(s) 10333–10339

    Abstract: Serotonin is an essential mediator regulating diverse neural processes, and its deregulation is related to the development of debilitating neurological diseases. In particular, the human serotonin transporter (hSERT) is fundamental in completing the ... ...

    Abstract Serotonin is an essential mediator regulating diverse neural processes, and its deregulation is related to the development of debilitating neurological diseases. In particular, the human serotonin transporter (hSERT) is fundamental in completing the synaptic neural cycle by allowing reuptake of serotonin. Its inhibition is particularly attractive, especially as a pharmacological target against depressive syndrome. Here, we analyze, by using long-range molecular dynamic simulations, the behavior of a molecular photoswitch whose
    MeSH term(s) Humans ; Biological Transport ; Molecular Dynamics Simulation ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/chemistry ; Serotonin Plasma Membrane Transport Proteins/metabolism
    Chemical Substances Serotonin (333DO1RDJY) ; Serotonin Plasma Membrane Transport Proteins ; SLC6A4 protein, human
    Language English
    Publishing date 2023-11-09
    Publishing country United States
    Document type Journal Article
    ISSN 1948-7185
    ISSN (online) 1948-7185
    DOI 10.1021/acs.jpclett.3c02655
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Molecular Basis of the pH-Controlled Maturation of the Tick-Borne Encephalitis Flavivirus.

    Bignon, Emmanuelle / Dumont, Elise / Monari, Antonio

    The journal of physical chemistry letters

    2023  Volume 14, Issue 7, Page(s) 1977–1982

    Abstract: Flaviviruses are enveloped viruses causing high public concerns. Their maturation spans several cellular compartments having different pH. Thus, complex control mechanisms are in place to avoid premature maturation. Here we report the dynamical behavior ... ...

    Abstract Flaviviruses are enveloped viruses causing high public concerns. Their maturation spans several cellular compartments having different pH. Thus, complex control mechanisms are in place to avoid premature maturation. Here we report the dynamical behavior at neutral and acidic pH of the precursor of the membrane fusion protein E of tick-borne encephalitis, showing the different stabilizations of the E dimer and the role played by the small fusion-assisting protomer (pr). The comprehension, at atomic resolution, of the fine regulation of viral maturation will be fundamental to the development of efficient strategies against emerging viral threats.
    MeSH term(s) Humans ; Encephalitis, Tick-Borne ; Encephalitis Viruses, Tick-Borne/chemistry ; Encephalitis Viruses, Tick-Borne/metabolism ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/metabolism ; Flavivirus Infections ; Hydrogen-Ion Concentration
    Chemical Substances Viral Envelope Proteins
    Language English
    Publishing date 2023-02-15
    Publishing country United States
    Document type Journal Article
    ISSN 1948-7185
    ISSN (online) 1948-7185
    DOI 10.1021/acs.jpclett.2c03551
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand.

    Hognon, Cécilia / Monari, Antonio

    Molecules (Basel, Switzerland)

    2021  Volume 26, Issue 13

    Abstract: Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer ... ...

    Abstract Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiotherapy and for immunotherapy. Despite its importance, its structure has been resolved only recently, and important questions concerning the arrangement of its active center, the interaction with the DNA substrate, and the catalytic mechanism remain unanswered. In this contribution, by performing extensive molecular dynamic simulations, both classically and at the hybrid quantum mechanics/molecular mechanics level, we evidenced the stable interaction modes of Artemis with a model DNA strand. We also analyzed the catalytic cycle providing the free energy profile and key transition states for the DNA cleavage reaction.
    MeSH term(s) DNA/chemistry ; DNA-Binding Proteins/chemistry ; Endonucleases/chemistry ; Humans ; Models, Chemical
    Chemical Substances DNA-Binding Proteins ; DNA (9007-49-2) ; DCLRE1C protein, human (EC 3.1.-) ; Endonucleases (EC 3.1.-)
    Language English
    Publishing date 2021-06-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules26133986
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top