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Molecular dynamics simulations provide structural insight into binding of cyclic dinucleotides to human STING protein

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F21%3A00556414" target="_blank" >RIV/86652036:_____/21:00556414 - isvavai.cz</a>

  • Alternative codes found

    RIV/61388963:_____/21:00556414

  • Result on the web

    <a href="https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1942213" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1942213</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1080/07391102.2021.1942213" target="_blank" >10.1080/07391102.2021.1942213</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Molecular dynamics simulations provide structural insight into binding of cyclic dinucleotides to human STING protein

  • Original language description

    Human stimulator of interferon genes (hSTING) is a signaling adaptor protein that triggers innate immune system by response to cytosolic DNA and second messenger cyclic dinucleotides (CDNs). Natural CDNs contain purine nucleobase with different phosphodiester linkage types (3 '-3 ', 2 '-2 ' or mixed 2 '-3 '-linkages) and exhibit different binding affinity towards hSTING, ranging from micromolar to nanomolar. High-affinity CDNs are considered as suitable candidates for treatment of chronic hepatitis B and cancer. We have used molecular dynamics simulations to investigate dynamical aspects of binding of natural CDNs (specifically, 2'-2'-cGAMP, 2'-3'-cGAMP, 3'-3'-cGAMP, 3'-3'-c-di-AMP, and 3'-3'-c-di-GMP) with hSTING(wt) protein. Our results revealed that CDN/hSTING(wt) interactions are controlled by the balance between fluctuations (conformational changes) in the CDN ligand and the protein dynamics. Binding of different CDNs induces different degrees of conformational/dynamics changes in hSTING(wt) ligand binding cavity, especially in alpha(1)-helices, the so-called lid region and alpha(2)-tails. The ligand residence time in hSTING(wt) protein pocket depends on different contribution of R232 and R238 residues interacting with oxygen atoms of phosphodiester groups in ligand, water distribution around interacting charged centers (in protein residues and ligand) and structural stability of closed conformation state of hSTING(wt) protein. These findings may perhaps guide design of new compounds modulating hSTING activity. Communicated by Ramaswamy H. Sarma

  • 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

    Journal of Biomolecular Structure & Dynamics

  • ISSN

    0739-1102

  • e-ISSN

  • Volume of the periodical

    JUN 2021

  • Issue of the periodical within the volume

    JUN 2021

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    16

  • Pages from-to

    2021-07-12

  • UT code for WoS article

    000668459800001

  • EID of the result in the Scopus database

    2-s2.0-85109015815