All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

Enzymatic Synthesis of 3′-5′, 3′-5′ Cyclic Dinucleotides, Their Binding Properties to the Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00549413" target="_blank" >RIV/61388963:_____/21:00549413 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11310/21:10437470

  • Result on the web

    <a href="https://doi.org/10.1021/acs.biochem.1c00692" target="_blank" >https://doi.org/10.1021/acs.biochem.1c00692</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1021/acs.biochem.1c00692" target="_blank" >10.1021/acs.biochem.1c00692</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Enzymatic Synthesis of 3′-5′, 3′-5′ Cyclic Dinucleotides, Their Binding Properties to the Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations

  • Original language description

    The 3′–5′, 3′–5′ cyclic dinucleotides (3′3′CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host innate immunity. Here, we profiled the substrate specificity of four bacterial dinucleotide synthases from Vibrio cholerae (DncV), Bacillus thuringiensis (btDisA), Escherichia coli (dgcZ), and Thermotoga maritima (tDGC) using a library of 33 nucleoside-5′-triphosphate analogues and then employed these enzymes to synthesize 24 3′3′CDNs. The STING affinity of CDNs was evaluated in cell-based and biochemical assays, and their ability to induce cytokines was determined by employing human peripheral blood mononuclear cells. Interestingly, the prepared heterodimeric 3′3′CDNs bound to the STING much better than their homodimeric counterparts and showed similar or better potency than bacterial 3′3′CDNs. We also rationalized the experimental findings by in-depth STING-CDN structure–activity correlations by dissecting computed interaction free energies into a set of well-defined and intuitive terms. To this aim, we employed state-of-the-art methods of computational chemistry, such as quantum mechanics/molecular mechanics (QM/MM) calculations, and complemented the computed results with the {STING:3′3′c-di-ara-AMP} X-ray crystallographic structure. QM/MM identified three outliers (mostly homodimers) for which we have no clear explanation of their impaired binding with respect to their heterodimeric counterparts, whereas the R2 = 0.7 correlation between the computed ΔG′int_rel and experimental ΔTm’s for the remaining ligands has been very encouraging.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2021

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Biochemistry

  • ISSN

    0006-2960

  • e-ISSN

  • Volume of the periodical

    60

  • Issue of the periodical within the volume

    48

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    14

  • Pages from-to

    3714-3727

  • UT code for WoS article

    000729443200005

  • EID of the result in the Scopus database

    2-s2.0-85119900415